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研究生:黃心穎
研究生(外文):Hsin-Ying Huang
論文名稱:探討過敏性氣喘的免疫及分子調控機制
論文名稱(外文):Study on Immune and Molecular Regulation of Allergic Asthmatic Disease
指導教授:江伯倫江伯倫引用關係
指導教授(外文):Bor-Luen Chiang
學位類別:博士
校院名稱:國立臺灣大學
系所名稱:免疫學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2009
畢業學年度:97
語文別:英文
論文頁數:128
中文關鍵詞:氣喘RNA干擾介白質-5嗜伊紅趨化原異體胜肽
外文關鍵詞:asthmashRNAIL-5eotaxinaltered peptide ligands
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過敏性氣喘起因於無害過敏原所引起的異常第二型T細胞(Th2)反應,這類異常的Th2反應被認為與第一型(Th1)與第二型T細胞反應的不平衡有關。嗜酸性白血球聚集(eosinophilia)在過敏性氣喘致病機制中中扮演重要的角色,且其嚴重程度與細胞激素interleukin 5 (IL-5)和趨化素eotaxin 的增加有關。嗜酸性白血球(eosinophils)所釋出之物質會傷害呼吸道上皮細胞、引起黏液的分泌以及平滑肌收縮進而引起呼吸道過渡反應(airway hyperresponsiveness, AHR)。IL-5對於嗜酸性白血球的從骨髓中分化、從骨髓釋出至周邊血以及嗜酸性白血球在組織中的活化和存活皆有重要的影響,而eotaxin則為吸引嗜酸性白血球至發炎組織和促進其於組織中活化及存活主要的趨化素。目前氣喘的治療方式主要是利用單株抗體或是蛋白質抑制劑來調節過敏反應,然而相較於直接調控蛋白質的功能,透過調控mRNA可以更有效調節基因表現。而近年來研究發現,RNA干擾(RNA interference)可以專一並有效抑制基因表現。本研究欲設計IL-5和eotaxin的專一性小片段RNA(short hairpin RNA, shRNA)並利用慢病毒載體(lentivirual vectors)將shRNA送入氣喘模式小鼠中,探討IL-5和eotaxin的shRNA在呼吸道發炎中的角色。首先,利用體外系統確認shRNA可以有效抑制IL-5以及eotaxin表現;進一步將帶有IL5 shRNA(IL5SEC4)或eotaxin shRNA(eoSEC3.3)的表現基因組(shRNA expressing cassette, SEC)的lentivirus在以卵清蛋白(ovalbumin, OVA)刺激小鼠前,以氣管注射(intratracheal, i.t.)的方式送入以OVA誘導氣喘的小鼠中。結果顯示局部、單次單獨給予IL5SEC4或eoSEC3.3皆可有效緩減呼吸道發炎反應,包括減緩嗜酸性白血球聚集和AHR,並有效減少肺泡沖洗液中IL-5和eotaxin的含量。且若合併給予兩種shRNAs(IL5SEC4+eoSEC3.3)亦可有效緩減氣喘模式小鼠的發炎反應,但相較於給予單一種shRNA之小鼠,合併兩種shRNAs並沒有更好的治療效果。儘管給予IL-5 或eotaxin shRNA可以有效抑制呼吸道發炎,但是對於血清中過敏原專一性免疫球蛋白E(immunoglobulin E, IgE)並無影響。
另外,Th1細胞及調節性T細胞(regulatory T cells, Tregs)被認為可以有效調控過敏原所引起之Th2反應;因此,在過敏氣喘的治療策略上,除了阻斷Th2反應外,誘導Th1細胞和Tregs是目前積極被研究作為氣喘治療的方向。研究指出修飾T細胞的抗原決定位(epitope peptide)之單一或數個胺基酸所產生之異體胜肽(altered peptide ligands, APLs)可能會大幅改變T細胞的功能,並指出APLs可以透過產生不同的細胞激素或是促使T細胞分化成不同型態來調節免疫反應。因此本研究欲利用OVA專一性的T細胞接受器(T cell receptor)基因轉質小鼠(DO11.10)之CD4 T細胞來研究APLs對於T細胞功能上的影響。本研究針對DO11.10 T細胞的主要epitope peptide加以修改,設計了六段單一胺基酸修飾的APLs(E333A,H331Q,H331F,H331R,H331E和 N335A),並以這些APLs刺激DO11.10 T細胞並測試T細胞的型態。其中五段APLs (E333A,H331Q,H331F,H331R和H331E)完全無法誘導T細胞增生、細胞激素分泌以及TCR內吞(internalization)。而N335A則可以在高濃度下刺激T細胞活化,由此結果推測N335A可能為弱增效劑(weak agonist)而其他五段APLs則為無效胜肽(null peptide)。此外,相較於WT刺激過之T細胞,N335A刺激過之T細胞在以WT peptide刺激下會分泌高量細胞激素IFN-γ以及較低的IL-4,推測N335A可能會誘導T細胞分化為Th1細胞。然而,六段APLs刺激過之T細胞完全沒有表現任何Treg相關之基因或功能。
本研究結果顯示局部給予IL-5或eotaxin shRNAs有潛力成為緩減呼吸道發炎的治療方式,並顯示可利用針對引起氣喘過敏反應之細胞激素或趨化素的shRNAs作為臨床治療方式可能性。而從體外試驗也找出可以誘導T細胞分化為Th1細胞之APL,接下來將把APL送入氣喘模式小鼠體內,以了解是否在體內APL是否可以達到改善過敏免疫的目的並了解是否可以透過誘導調節性免疫反應而有效地抑制呼吸道的發炎反應。
Asthma is caused by aberrant Th2 responses to harmless inhaled allergens underlaid a disturbance in the balance between Th1- and Th2-mediated immune responses. Eosinophilia plays the major role in the pathogenesis of asthma and correlates with the up-regulation of eotaxin, which, together with interleukin (IL)-5, is important for differentiation, chemo-attraction, degranulation, and survival of eosinophils in local tissue. Mediators released by eosinophils directly damage the epithelium cells and induce smooth muscles constriction and mucus secretion, subsequently result in airway hyperresponsiveness. Many therapeutic strategies for asthma are based on modulating the allergic responses through antibody or inhibitor. However, gene regulation in mRNA levels is more efficient than in protein levels. Recently, RNAi has been shown to be an efficacious in transcriptional or posttranscriptional silencing target genes. The present study aimed to investigate the role of eotaxin and IL-5 short hairpin RNAs (shRNAs) and their synergistic effect on airway inflammation in an ovalbumin (OVA)-induced murine model of asthma. Lentivirus-delivered shRNAs were used to suppress the expression of eotaxin and/or IL-5 in local tissue and we found that intra-tracheal administration of lentivirus containing eotaxin or IL-5 shRNAs expressing cassette (eoSEC3.3 or IL5SEC4) efficiently moderated the characteristics of asthma, including airway hyper-responsiveness, cellular infiltration of lung tissues, and eotaxin and IL-5 levels in bronchio-alveolar lavage fluid. concomitant administration of lentiviruses expressing IL-5 and eotaxin shRNAs (IL5SEC4 + eoSEC3.3) also moderated the symptoms of asthma in a mouse model. However, there was no effect on OVA-specific IgE level neither in single shRNA treated mice nor combination of eotxin and IL-5 shRNAs treated ones.
In addition, Th1 cells and regulatory T cells are thought to modulate the allergen-induced Th2 responses. Peptide alterations of T cell epitopes with single or few amino acid variations can have drastic effects on the outcome of this recognition. Altered peptide ligands (APLs) can act as modulators of immune responses through induction of different cytokines production profile or differentiation of different lineage of T cells. In this study, we would like to design APLs, which modified from OVA323-339 peptide, major epitope of DO11.10 TCR transgenic mice, and investigate whether APLs affect the function of allergen-specific T cells, such as differentiating toward Treg or Th1 and then we will investigate whether APLs could modulate the airway inflammation in OVA-induced murine of asthma mice, as an allergen-specific immunotherapy approach. We synthesized six APLs with a single amino acid substitution of the OVA323-339 (WT) and examined the phenotypes of OVA-specific T cells activated by these peptide analogues. In our results, five of six peptide analogues (E333A, H331Q, H331F, H331R, and H331E,) did not induce proliferation, TCR internalization, and cytokines production of DO11.10 T cells, being null peptides. Whereas, N335A induced activation of T cells in high concentration, likely being a weak agonist. Furthermore, N335A-primed T cells produced higher level of INF-γ and lower level of IL-4 compared with WT-primed T cells upon WT restimulation, indicating that N335A likely skewed T cells toward Th1 cells. However, T cells stimulated with six peptide analogues did not show any properties of Treg cells.
In our study, local delivery of lentiviruses expressing IL-5 and eotaxin shRNAs provides a potential tool in moderating airway inflammation and also has the potential for developing clinical therapy based on the application of shRNAs of chemokines and cytokines involved in T helper 2 cell inflammation and eosinophilia. In addition, we found that the OVA peptide analogous, N335A, could induce OVA-specific T cells to differentiate into Th1 cells and then we will deliver N335A into OVA-sensitized mice to investigate whether N335A could regulate the allergic responses and inhibit the airway inflammation in murine model of asthma.
ABSTRACTS i
中文摘要 iv
ABBREVIATIONS vi
CONTENTS vii
CONTENTS OF TABLES xi
CONTENTS OF FIGURES xii

GENERAL INTRODUCITON OF ASTHMA 1
1 An overview of Asthma 2
2 The mechanisms of allergic asthma 2
2.1 T cells response of asthma 3
2.1.1 Th2 cells and cytokines 3
2.1.2 Th1/Th2 balance 5
2.1.3 Regulatory T cells (Tregs) in asthma 6
2.2 Eosinophils 9
2.3 Interleukin-5 (IL-5) 10
2.4 Eotxin 10
2.5 Airway hyperresponsiveness (AHR) 11
3 Approaches to the treatment of asthma 12
4 Aims of the study 13

PART I Small Interfering RNA Against Interleukin-5 and Eotaxin Decreases Airway Eosinophilia and Hyperresponsiveness
CHAPTER I Introduction 16
1.1 RNA interference (RNAi) 17
1.1.1 The mechanism of RNAi 17
1.1.2 siRNA in asthma therapy 17
1.1.3 Off-target effects and unintended responses of RNAi 18
1.1.4 Approaches to minimize off-target effects 21
1.2 Lentiviral vectors 22
1.2.1 The development of lentiviral vector 22
1.2.2 Lentiviral-mediated delivery of shRNAs 24
1.2.3 Lentiviral vectors as a therapeutic tool 25
1.3 Aims of the study 26
CHAPTER II Materials and Methods 27
2.1 Construction of shRNA expression cassettes (SECs) 28
2.2 Preparation of SEC-expressing lentiviruses 28
2.3 Determination of suppression efficiency of SECs in vitro 29
2.3.1 Determination of suppression efficiency of IL-5 shRNAs in vitro 29
2.3.2 Determination of suppression efficiency of eotaxin shRNAs in vitro 29
2.4 Mice 30
2.5 OVA-induced allergic airway inflammation 30
2.6 Airway function determination 30
2.6.1 Non-invasive whole body plethysmography 30
2.6.2 Invasive body plethysmography 31
2.7 OVA-specific antibody assay 31
2.8 Bronchoalveolar lavage fluid 32
2.9 Histological examination of lung sections 32
2.10 Determination of cytokine expression 33
2.11 Real-time quantitative PCR 33
2.12 Statistical analysis 33
CHAPTER III Results 34
3.1 In vitro characterization of shRNA targeting to murine IL-5 35
3.2 IL-5 mRNA level knock-down in vivo 35
3.3 Reduction of airway hyper-responsiveness and eosinophilia by IL-5 shRNA-expressing lentiviruses 36
3.4 IL5SEC4 suppressed eosinophil chemoattractive chemokine, eotaxin, in BAL fluid 37
3.5 In vitro characterization of shRNA targeting to murine eotaxin 37
3.6 Intra-tracheal delivery of eotaxin-shRNAs decreased airway hyperresponsiveness 38
3.7 Inhibition of eosinophilia by eotaxin shRNA-expressing lentiviruses 38
3.8 eoSEC3.3 suppressed IL-5 and eotaxin in BAL fluid 39
3.9 Delivery of SEC-containing lentiviruses did not affect sera allergen-specific immunoglobulin levels 39
CHAPTER IV Discussion 40

PART II The role of altered peptide ligands in induction of tolerance in OVA-induced murine model of asthma
CHAPTER I Introduction 48
1.1 Altered peptide ligands (APLs) 49
1.1.1 Altered peptide ligands (APLs) and T cell activation 49
1.1.2 The design of APLs 50
1.1.3 The mechanisms in APL immunotherapy 50
1.2 Aims of study 51
CHAPTER II Materials and Methods 53
2.1 Mice 54
2.2 Synthetic peptides 54
2.3 Isolation of CD4+ T cells 54
2.4 Activation of DO11.10 T cells 54
2.4.1 Primary stimulation of T cells 54
2.4.2 T cell proliferation assay 55
2.4.3 Restimulation of T cells 55
2.5 Cytokine assay 55
2.6 The level of TCR downmodulation 55
2.7 Competition assay 56
2.8 Real-time quantitative PCR 56
CHAPTER III Results 57
3.1 Design of OVA323-339 peptide analogues 58
3.2 Characterization of OVA323-339 peptide analogues 58
3.3 Functional characterization of N335A-treated T cells 59
CHPATER IV Discussion 61

CONCLUSION AND FUTURE PROSPECTS 64
TABLES 68
FIGURES 70
REFERENCE 97
APPENDIX 123
Abbas-Terki, T., Blanco-Bose, W., Deglon, N., Pralong, W., and Aebischer, P. (2002). Lentiviral-mediated RNA interference. Hum Gene Ther 13, 2197-2201.
Akbari, O., DeKruyff, R.H., and Umetsu, D.T. (2001). Pulmonary dendritic cells producing IL-10 mediate tolerance induced by respiratory exposure to antigen. Nat Immunol 2, 725-731.
Akbari, O., Freeman, G.J., Meyer, E.H., Greenfield, E.A., Chang, T.T., Sharpe, A.H., Berry, G., DeKruyff, R.H., and Umetsu, D.T. (2002). Antigen-specific regulatory T cells develop via the ICOS-ICOS-ligand pathway and inhibit allergen-induced airway hyperreactivity. Nat Med 8, 1024-1032.
Akdis, M., Verhagen, J., Taylor, A., Karamloo, F., Karagiannidis, C., Crameri, R., Thunberg, S., Deniz, G., Valenta, R., Fiebig, H., et al. (2004). Immune responses in healthy and allergic individuals are characterized by a fine balance between allergen-specific T regulatory 1 and T helper 2 cells. J Exp Med 199, 1567-1575.
Alleva, D.G., Gaur, A., Jin, L., Wegmann, D., Gottlieb, P.A., Pahuja, A., Johnson, E.B., Motheral, T., Putnam, A., Crowe, P.D., et al. (2002). Immunological characterization and therapeutic activity of an altered-peptide ligand, NBI-6024, based on the immunodominant type 1 diabetes autoantigen insulin B-chain (9-23) peptide. Diabetes 51, 2126-2134.
Andreadis, S.T., Brott, D., Fuller, A.O., and Palsson, B.O. (1997). Moloney murine leukemia virus-derived retroviral vectors decay intracellularly with a half-life in the range of 5.5 to 7.5 hours. J Virol 71, 7541-7548.
Arock, M., Zuany-Amorim, C., Singer, M., Benhamou, M., and Pretolani, M. (1996). Interleukin-10 inhibits cytokine generation from mast cells. Eur J Immunol 26, 166-170.
Babbitt, B.P., Allen, P.M., Matsueda, G., Haber, E., and Unanue, E.R. (1985). Binding of immunogenic peptides to Ia histocompatibility molecules. Nature 317, 359-361.
Bacchetta, R., Bigler, M., Touraine, J.L., Parkman, R., Tovo, P.A., Abrams, J., de Waal Malefyt, R., de Vries, J.E., and Roncarolo, M.G. (1994). High levels of interleukin 10 production in vivo are associated with tolerance in SCID patients transplanted with HLA mismatched hematopoietic stem cells. J Exp Med 179, 493-502.
Balzar, S., Strand, M., Rhodes, D., and Wenzel, S.E. (2007). IgE expression pattern in lung: relation to systemic IgE and asthma phenotypes. J Allergy Clin Immunol 119, 855-862.
Basu, D., Williams, C.B., and Allen, P.M. (1998). In vivo antagonism of a T cell response by an endogenously expressed ligand. Proc Natl Acad Sci U S A 95, 14332-14336.
Bellinghausen, I., Klostermann, B., Knop, J., and Saloga, J. (2003). Human CD4+CD25+ T cells derived from the majority of atopic donors are able to suppress TH1 and TH2 cytokine production. J Allergy Clin Immunol 111, 862-868.
Ben-David, H., Sela, M., and Mozes, E. (2005). Down-regulation of myasthenogenic T cell responses by a dual altered peptide ligand via CD4+CD25+-regulated events leading to apoptosis. Proc Natl Acad Sci U S A 102, 2028-2033.
Bertoletti, A., Sette, A., Chisari, F.V., Penna, A., Levrero, M., De Carli, M., Fiaccadori, F., and Ferrari, C. (1994). Natural variants of cytotoxic epitopes are T-cell receptor antagonists for antiviral cytotoxic T cells. Nature 369, 407-410.
Bielekova, B., and Martin, R. (2001). Antigen-specific immunomodulation via altered peptide ligands. J Mol Med 79, 552-565.
Blanchard, C., Mishra, A., Saito-Akei, H., Monk, P., Anderson, I., and Rothenberg, M.E. (2005). Inhibition of human interleukin-13-induced respiratory and oesophageal inflammation by anti-human-interleukin-13 antibody (CAT-354). Clin Exp Allergy 35, 1096-1103.
Borchers, M.T., Crosby, J., Justice, P., Farmer, S., Hines, E., Lee, J.J., and Lee, N.A. (2001). Intrinsic AHR in IL-5 transgenic mice is dependent on CD4(+) cells and CD49d-mediated signaling. Am J Physiol Lung Cell Mol Physiol 281, L653-659.
Borish, L.C., Nelson, H.S., Lanz, M.J., Claussen, L., Whitmore, J.B., Agosti, J.M., and Garrison, L. (1999). Interleukin-4 receptor in moderate atopic asthma. A phase I/II randomized, placebo-controlled trial. Am J Respir Crit Care Med 160, 1816-1823.
Boushey, H.A. (1982). Bronchial hyperreactivity to sulfur dioxide: physiologic and political implications. J Allergy Clin Immunol 69, 335-338.
Bousquet, J., Chanez, P., Lacoste, J.Y., Barneon, G., Ghavanian, N., Enander, I., Venge, P., Ahlstedt, S., Simony-Lafontaine, J., Godard, P., and et al. (1990). Eosinophilic inflammation in asthma. N Engl J Med 323, 1033-1039.
Breckpot, K., Aerts, J.L., and Thielemans, K. (2007). Lentiviral vectors for cancer immunotherapy: transforming infectious particles into therapeutics. Gene Ther 14, 847-862.
Bridge, A.J., Pebernard, S., Ducraux, A., Nicoulaz, A.L., and Iggo, R. (2003). Induction of an interferon response by RNAi vectors in mammalian cells. Nat Genet 34, 263-264.
Brightling, C.E., Bradding, P., Symon, F.A., Holgate, S.T., Wardlaw, A.J., and Pavord, I.D. (2002). Mast-cell infiltration of airway smooth muscle in asthma. N Engl J Med 346, 1699-1705.
Brocke, S., Gijbels, K., Allegretta, M., Ferber, I., Piercy, C., Blankenstein, T., Martin, R., Utz, U., Karin, N., Mitchell, D., et al. (1996). Treatment of experimental encephalomyelitis with a peptide analogue of myelin basic protein. Nature 379, 343-346.
Brown, B.D., Sitia, G., Annoni, A., Hauben, E., Sergi, L.S., Zingale, A., Roncarolo, M.G., Guidotti, L.G., and Naldini, L. (2007). In vivo administration of lentiviral vectors triggers a type I interferon response that restricts hepatocyte gene transfer and promotes vector clearance. Blood 109, 2797-2805.
Brusselle, G., Kips, J., Joos, G., Bluethmann, H., and Pauwels, R. (1995). Allergen-induced airway inflammation and bronchial responsiveness in wild-type and interleukin-4-deficient mice. Am J Respir Cell Mol Biol 12, 254-259.
Brusselle, G.G., Kips, J.C., Tavernier, J.H., van der Heyden, J.G., Cuvelier, C.A., Pauwels, R.A., and Bluethmann, H. (1994). Attenuation of allergic airway inflammation in IL-4 deficient mice. Clin Exp Allergy 24, 73-80.
Burns, J.C., Friedmann, T., Driever, W., Burrascano, M., and Yee, J.K. (1993). Vesicular stomatitis virus G glycoprotein pseudotyped retroviral vectors: concentration to very high titer and efficient gene transfer into mammalian and nonmammalian cells. Proc Natl Acad Sci U S A 90, 8033-8037.
Busse, W.W., and Lemanske, R.F., Jr. (2001). Asthma. N Engl J Med 344, 350-362.
Buttner, C., Lun, A., Splettstoesser, T., Kunkel, G., and Renz, H. (2003). Monoclonal anti-interleukin-5 treatment suppresses eosinophil but not T-cell functions. Eur Respir J 21, 799-803.
Chang, L.J., Urlacher, V., Iwakuma, T., Cui, Y., and Zucali, J. (1999). Efficacy and safety analyses of a recombinant human immunodeficiency virus type 1 derived vector system. Gene Ther 6, 715-728.
Chen, T.C., Waldmann, H., and Fairchild, P.J. (2004). Induction of dominant transplantation tolerance by an altered peptide ligand of the male antigen Dby. J Clin Invest 113, 1754-1762.
Chen, Y.Z., Lai, Z.F., Nishi, K., and Nishimura, Y. (1998). Modulation of calcium responses by altered peptide ligands in a human T cell clone. Eur J Immunol 28, 3929-3939.
Chiaramonte, M.G., Schopf, L.R., Neben, T.Y., Cheever, A.W., Donaldson, D.D., and Wynn, T.A. (1999). IL-13 is a key regulatory cytokine for Th2 cell-mediated pulmonary granuloma formation and IgE responses induced by Schistosoma mansoni eggs. J Immunol 162, 920-930.
Chuang, Y.H., Fu, C.L., Lo, Y.C., and Chiang, B.L. (2004). Adenovirus expressing Fas ligand gene decreases airway hyper-responsiveness and eosinophilia in a murine model of asthma. Gene Ther 11, 1497-1505.
Cockcroft, D.W., and Davis, B.E. (2006). Mechanisms of airway hyperresponsiveness. J Allergy Clin Immunol 118, 551-559; quiz 560-551.
Cohn, L., Homer, R.J., Marinov, A., Rankin, J., and Bottomly, K. (1997). Induction of airway mucus production by T helper 2 (Th2) cells: a critical role for interleukin 4 in cell recruitment but not mucus production. J Exp Med 186, 1737-1747.
Cohn, L., Elias, J.A., and Chupp, G.L. (2004). Asthma: mechanisms of disease persistence and progression. Annu Rev Immunol 22, 789-815.
Coil, D.A., and Miller, A.D. (2004). Phosphatidylserine is not the cell surface receptor for vesicular stomatitis virus. J Virol 78, 10920-10926.
Collins, P.D., Marleau, S., Griffiths-Johnson, D.A., Jose, P.J., and Williams, T.J. (1995). Cooperation between interleukin-5 and the chemokine eotaxin to induce eosinophil accumulation in vivo. J Exp Med 182, 1169-1174.
Corry, D.B., Folkesson, H.G., Warnock, M.L., Erle, D.J., Matthay, M.A., Wiener-Kronish, J.P., and Locksley, R.M. (1996). Interleukin 4, but not interleukin 5 or eosinophils, is required in a murine model of acute airway hyperreactivity. J Exp Med 183, 109-117.
Coyle, A.J., Le Gros, G., Bertrand, C., Tsuyuki, S., Heusser, C.H., Kopf, M., and Anderson, G.P. (1995). Interleukin-4 is required for the induction of lung Th2 mucosal immunity. Am J Respir Cell Mol Biol 13, 54-59.
Cui, Y., Iwakuma, T., and Chang, L.J. (1999). Contributions of viral splice sites and cis-regulatory elements to lentivirus vector function. J Virol 73, 6171-6176.
Daniels, S.E., Bhattacharrya, S., James, A., Leaves, N.I., Young, A., Hill, M.R., Faux, J.A., Ryan, G.F., le Souef, P.N., Lathrop, G.M., et al. (1996). A genome-wide search for quantitative trait loci underlying asthma. Nature 383, 247-250.
De Magistris, M.T., Alexander, J., Coggeshall, M., Altman, A., Gaeta, F.C., Grey, H.M., and Sette, A. (1992). Antigen analog-major histocompatibility complexes act as antagonists of the T cell receptor. Cell 68, 625-634.
de Vries, J.E. (1998). The role of IL-13 and its receptor in allergy and inflammatory responses. J Allergy Clin Immunol 102, 165-169.
Delenda, C. (2004). Lentiviral vectors: optimization of packaging, transduction and gene expression. J Gene Med 6 Suppl 1, S125-138.
Dent, L.A., Strath, M., Mellor, A.L., and Sanderson, C.J. (1990). Eosinophilia in transgenic mice expressing interleukin 5. J Exp Med 172, 1425-1431.
Dorman, S.C., Sehmi, R., Gauvreau, G.M., Watson, R.M., Foley, R., Jones, G.L., Denburg, J.A., Inman, M.D., and O''Byrne, P.M. (2004). Kinetics of bone marrow eosinophilopoiesis and associated cytokines after allergen inhalation. Am J Respir Crit Care Med 169, 565-572.
Dubucquoi, S., Desreumaux, P., Janin, A., Klein, O., Goldman, M., Tavernier, J., Capron, A., and Capron, M. (1994). Interleukin 5 synthesis by eosinophils: association with granules and immunoglobulin-dependent secretion. J Exp Med 179, 703-708.
Dull, T., Zufferey, R., Kelly, M., Mandel, R.J., Nguyen, M., Trono, D., and Naldini, L. (1998). A third-generation lentivirus vector with a conditional packaging system. J Virol 72, 8463-8471.
Elbashir, S.M., Harborth, J., Lendeckel, W., Yalcin, A., Weber, K., and Tuschl, T. (2001). Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411, 494-498.
Emson, C.L., Bell, S.E., Jones, A., Wisden, W., and McKenzie, A.N. (1998). Interleukin (IL)-4-independent induction of immunoglobulin (Ig)E, and perturbation of T cell development in transgenic mice expressing IL-13. J Exp Med 188, 399-404.
Esslinger, C., Chapatte, L., Finke, D., Miconnet, I., Guillaume, P., Levy, F., and MacDonald, H.R. (2003). In vivo administration of a lentiviral vaccine targets DCs and induces efficient CD8(+) T cell responses. J Clin Invest 111, 1673-1681.
Evavold, B.D., Sloan-Lancaster, J., Hsu, B.L., and Allen, P.M. (1993). Separation of T helper 1 clone cytolysis from proliferation and lymphokine production using analog peptides. J Immunol 150, 3131-3140.
Evavold, B.D., Williams, S.G., Hsu, B.L., Buus, S., and Allen, P.M. (1992). Complete dissection of the Hb(64-76) determinant using T helper 1, T helper 2 clones, and T cell hybridomas. J Immunol 148, 347-353.
Farahi, N., Cowburn, A.S., Upton, P.D., Deighton, J., Sobolewski, A., Gherardi, E., Morrell, N.W., and Chilvers, E.R. (2007). Eotaxin-1/CC chemokine ligand 11: a novel eosinophil survival factor secreted by human pulmonary artery endothelial cells. J Immunol 179, 1264-1273.
Filley, W.V., Holley, K.E., Kephart, G.M., and Gleich, G.J. (1982). Identification by immunofluorescence of eosinophil granule major basic protein in lung tissues of patients with bronchial asthma. Lancet 2, 11-16.
Finotto, S., De Sanctis, G.T., Lehr, H.A., Herz, U., Buerke, M., Schipp, M., Bartsch, B., Atreya, R., Schmitt, E., Galle, P.R., et al. (2001). Treatment of allergic airway inflammation and hyperresponsiveness by antisense-induced local blockade of GATA-3 expression. J Exp Med 193, 1247-1260.
Finotto, S., Neurath, M.F., Glickman, J.N., Qin, S., Lehr, H.A., Green, F.H., Ackerman, K., Haley, K., Galle, P.R., Szabo, S.J., et al. (2002). Development of spontaneous airway changes consistent with human asthma in mice lacking T-bet. Science 295, 336-338.
Fire, A., Xu, S., Montgomery, M.K., Kostas, S.A., Driver, S.E., and Mello, C.C. (1998). Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391, 806-811.
Flood-Page, P., Swenson, C., Faiferman, I., Matthews, J., Williams, M., Brannick, L., Robinson, D., Wenzel, S., Busse, W., Hansel, T.T., and Barnes, N.C. (2007). A study to evaluate safety and efficacy of mepolizumab in patients with moderate persistent asthma. Am J Respir Crit Care Med 176, 1062-1071.
Fontenot, J.D., Gavin, M.A., and Rudensky, A.Y. (2003). Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol 4, 330-336.
Foster, P.S., Hogan, S.P., Ramsay, A.J., Matthaei, K.I., and Young, I.G. (1996). Interleukin 5 deficiency abolishes eosinophilia, airways hyperreactivity, and lung damage in a mouse asthma model. J Exp Med 183, 195-201.
Fujisawa, T., Kato, Y., Nagase, H., Atsuta, J., Terada, A., Iguchi, K., Kamiya, H., Morita, Y., Kitaura, M., Kawasaki, H., et al. (2000). Chemokines induce eosinophil degranulation through CCR-3. J Allergy Clin Immunol 106, 507-513.
Garrett, J.K., Jameson, S.C., Thomson, B., Collins, M.H., Wagoner, L.E., Freese, D.K., Beck, L.A., Boyce, J.A., Filipovich, A.H., Villanueva, J.M., et al. (2004). Anti-interleukin-5 (mepolizumab) therapy for hypereosinophilic syndromes. J Allergy Clin Immunol 113, 115-119.
Gavett, S.H., O''Hearn, D.J., Karp, C.L., Patel, E.A., Schofield, B.H., Finkelman, F.D., and Wills-Karp, M. (1997). Interleukin-4 receptor blockade prevents airway responses induced by antigen challenge in mice. Am J Physiol 272, L253-261.
Gevaert, P., Lang-Loidolt, D., Lackner, A., Stammberger, H., Staudinger, H., Van Zele, T., Holtappels, G., Tavernier, J., van Cauwenberge, P., and Bachert, C. (2006). Nasal IL-5 levels determine the response to anti-IL-5 treatment in patients with nasal polyps. J Allergy Clin Immunol 118, 1133-1141.
Ginn, S.L., Fleming, J., Rowe, P.B., and Alexander, I.E. (2003). Promoter interference mediated by the U3 region in early-generation HIV-1-derived lentivirus vectors can influence detection of transgene expression in a cell-type and species-specific manner. Hum Gene Ther 14, 1127-1137.
Glaab, T., Mitzner, W., Braun, A., Ernst, H., Korolewitz, R., Hohlfeld, J.M., Krug, N., and Hoymann, H.G. (2004). Repetitive measurements of pulmonary mechanics to inhaled cholinergic challenge in spontaneously breathing mice. J Appl Physiol 97, 1104-1111.
Grimm, D., Streetz, K.L., Jopling, C.L., Storm, T.A., Pandey, K., Davis, C.R., Marion, P., Salazar, F., and Kay, M.A. (2006). Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways. Nature 441, 537-541.
Grindebacke, H., Wing, K., Andersson, A.C., Suri-Payer, E., Rak, S., and Rudin, A. (2004). Defective suppression of Th2 cytokines by CD4CD25 regulatory T cells in birch allergics during birch pollen season. Clin Exp Allergy 34, 1364-1372.
Groux, H., O''Garra, A., Bigler, M., Rouleau, M., Antonenko, S., de Vries, J.E., and Roncarolo, M.G. (1997). A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature 389, 737-742.
Grunig, G., Warnock, M., Wakil, A.E., Venkayya, R., Brombacher, F., Rennick, D.M., Sheppard, D., Mohrs, M., Donaldson, D.D., Locksley, R.M., and Corry, D.B. (1998). Requirement for IL-13 independently of IL-4 in experimental asthma. Science 282, 2261-2263.
Gu, W., Putral, L., and McMillan, N. (2008). siRNA and shRNA as anticancer agents in a cervical cancer model. Methods Mol Biol 442, 159-172.
Hadeiba, H., and Locksley, R.M. (2003). Lung CD25 CD4 regulatory T cells suppress type 2 immune responses but not bronchial hyperreactivity. J Immunol 170, 5502-5510.
Hamelmann, E., Schwarze, J., Takeda, K., Oshiba, A., Larsen, G.L., Irvin, C.G., and Gelfand, E.W. (1997). Noninvasive measurement of airway responsiveness in allergic mice using barometric plethysmography. Am J Respir Crit Care Med 156, 766-775.
Hart, T.K., Blackburn, M.N., Brigham-Burke, M., Dede, K., Al-Mahdi, N., Zia-Amirhosseini, P., and Cook, R.M. (2002). Preclinical efficacy and safety of pascolizumab (SB 240683): a humanized anti-interleukin-4 antibody with therapeutic potential in asthma. Clin Exp Immunol 130, 93-100.
Hawrylowicz, C.M., and O''Garra, A. (2005). Potential role of interleukin-10-secreting regulatory T cells in allergy and asthma. Nat Rev Immunol 5, 271-283.
Heaton, T., Rowe, J., Turner, S., Aalberse, R.C., de Klerk, N., Suriyaarachchi, D., Serralha, M., Holt, B.J., Hollams, E., Yerkovich, S., et al. (2005). An immunoepidemiological approach to asthma: identification of in-vitro T-cell response patterns associated with different wheezing phenotypes in children. Lancet 365, 142-149.
Heidel, J.D., Yu, Z., Liu, J.Y., Rele, S.M., Liang, Y., Zeidan, R.K., Kornbrust, D.J., and Davis, M.E. (2007). Administration in non-human primates of escalating intravenous doses of targeted nanoparticles containing ribonucleotide reductase subunit M2 siRNA. Proc Natl Acad Sci U S A 104, 5715-5721.
Heil, F., Hemmi, H., Hochrein, H., Ampenberger, F., Kirschning, C., Akira, S., Lipford, G., Wagner, H., and Bauer, S. (2004). Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8. Science 303, 1526-1529.
Heinonen, J.E., Smith, C.I., and Nore, B.F. (2002). Silencing of Bruton''s tyrosine kinase (Btk) using short interfering RNA duplexes (siRNA). FEBS Lett 527, 274-278.
Holgate, S.T., Djukanovic, R., Casale, T., and Bousquet, J. (2005). Anti-immunoglobulin E treatment with omalizumab in allergic diseases: an update on anti-inflammatory activity and clinical efficacy. Clin Exp Allergy 35, 408-416.
Hori, S., Nomura, T., and Sakaguchi, S. (2003). Control of regulatory T cell development by the transcription factor Foxp3. Science 299, 1057-1061.
Hornung, V., Guenthner-Biller, M., Bourquin, C., Ablasser, A., Schlee, M., Uematsu, S., Noronha, A., Manoharan, M., Akira, S., de Fougerolles, A., et al. (2005). Sequence-specific potent induction of IFN-alpha by short interfering RNA in plasmacytoid dendritic cells through TLR7. Nat Med 11, 263-270.
Hu-Lieskovan, S., Heidel, J.D., Bartlett, D.W., Davis, M.E., and Triche, T.J. (2005). Sequence-specific knockdown of EWS-FLI1 by targeted, nonviral delivery of small interfering RNA inhibits tumor growth in a murine model of metastatic Ewing''s sarcoma. Cancer Res 65, 8984-8992.
Huang, H.Y., Lee, C.C., and Chiang, B.L. (2008). Small interfering RNA against interleukin-5 decreases airway eosinophilia and hyper-responsiveness. Gene Ther 15, 660-667.
Huang, H.Y., Lee, C.C., and Chiang, B.L. (2009). Short hairpin RNAs against eotaxin or interleukin-5 decrease airway eosinophilia and hyper-responsiveness in a murine model of asthma. J Gene Med 11, 112-118.
Huang, T.J., MacAry, P.A., Eynott, P., Moussavi, A., Daniel, K.C., Askenase, P.W., Kemeny, D.M., and Chung, K.F. (2001). Allergen-specific Th1 cells counteract efferent Th2 cell-dependent bronchial hyperresponsiveness and eosinophilic inflammation partly via IFN-gamma. J Immunol 166, 207-217.
Humbert, M., Corrigan, C.J., Kimmitt, P., Till, S.J., Kay, A.B., and Durham, S.R. (1997). Relationship between IL-4 and IL-5 mRNA expression and disease severity in atopic asthma. Am J Respir Crit Care Med 156, 704-708.
Hutvagner, G., Simard, M.J., Mello, C.C., and Zamore, P.D. (2004). Sequence-specific inhibition of small RNA function. PLoS Biol 2, E98.
Illes, Z., Stern, J.N., Reddy, J., Waldner, H., Mycko, M.P., Brosnan, C.F., Ellmerich, S., Altmann, D.M., Santambrogio, L., Strominger, J.L., and Kuchroo, V.K. (2004). Modified amino acid copolymers suppress myelin basic protein 85-99-induced encephalomyelitis in humanized mice through different effects on T cells. Proc Natl Acad Sci U S A 101, 11749-11754.
Ishimoto, T., Takei, Y., Yuzawa, Y., Hanai, K., Nagahara, S., Tarumi, Y., Matsuo, S., and Kadomatsu, K. (2008). Downregulation of monocyte chemoattractant protein-1 involving short interfering RNA attenuates hapten-induced contact hypersensitivity. Mol Ther 16, 387-395.
Iwakuma, T., Cui, Y., and Chang, L.J. (1999). Self-inactivating lentiviral vectors with U3 and U5 modifications. Virology 261, 120-132.
Jackson, A.L., Bartz, S.R., Schelter, J., Kobayashi, S.V., Burchard, J., Mao, M., Li, B., Cavet, G., and Linsley, P.S. (2003). Expression profiling reveals off-target gene regulation by RNAi. Nat Biotechnol 21, 635-637.
Jacoby, D.B., Gleich, G.J., and Fryer, A.D. (1993). Human eosinophil major basic protein is an endogenous allosteric antagonist at the inhibitory muscarinic M2 receptor. J Clin Invest 91, 1314-1318.
Jaffar, Z., Sivakuru, T., and Roberts, K. (2004). CD4+CD25+ T cells regulate airway eosinophilic inflammation by modulating the Th2 cell phenotype. J Immunol 172, 3842-3849.
Janssen, E.M., van Oosterhout, A.J., van Rensen, A.J., van Eden, W., Nijkamp, F.P., and Wauben, M.H. (2000). Modulation of Th2 responses by peptide analogues in a murine model of allergic asthma: amelioration or deterioration of the disease process depends on the Th1 or Th2 skewing characteristics of the therapeutic peptide. J Immunol 164, 580-588.
Jeannin, P., Lecoanet, S., Delneste, Y., Gauchat, J.F., and Bonnefoy, J.Y. (1998). IgE versus IgG4 production can be differentially regulated by IL-10. J Immunol 160, 3555-3561.
Jeffery, P.K., Wardlaw, A.J., Nelson, F.C., Collins, J.V., and Kay, A.B. (1989). Bronchial biopsies in asthma. An ultrastructural, quantitative study and correlation with hyperreactivity. Am Rev Respir Dis 140, 1745-1753.
Judge, A.D., Sood, V., Shaw, J.R., Fang, D., McClintock, K., and MacLachlan, I. (2005). Sequence-dependent stimulation of the mammalian innate immune response by synthetic siRNA. Nat Biotechnol 23, 457-462.
Justice, J.P., Borchers, M.T., Crosby, J.R., Hines, E.M., Shen, H.H., Ochkur, S.I., McGarry, M.P., Lee, N.A., and Lee, J.J. (2003). Ablation of eosinophils leads to a reduction of allergen-induced pulmonary pathology. Am J Physiol Lung Cell Mol Physiol 284, L169-178.
Karras, J.G., McGraw, K., McKay, R.A., Cooper, S.R., Lerner, D., Lu, T., Walker, C., Dean, N.M., and Monia, B.P. (2000). Inhibition of antigen-induced eosinophilia and late phase airway hyperresponsiveness by an IL-5 antisense oligonucleotide in mouse models of asthma. J Immunol 164, 5409-5415.
Kawasaki, H., and Taira, K. (2004). Induction of DNA methylation and gene silencing by short interfering RNAs in human cells. Nature 431, 211-217.
Kawasaki, H., Taira, K., and Morris, K.V. (2005). siRNA induced transcriptional gene silencing in mammalian cells. Cell Cycle 4, 442-448.
Kay, A.B., Phipps, S., and Robinson, D.S. (2004). A role for eosinophils in airway remodelling in asthma. Trends Immunol 25, 477-482.
Kearley, J., Barker, J.E., Robinson, D.S., and Lloyd, C.M. (2005). Resolution of airway inflammation and hyperreactivity after in vivo transfer of CD4+CD25+ regulatory T cells is interleukin 10 dependent. J Exp Med 202, 1539-1547.
Khattri, R., Cox, T., Yasayko, S.A., and Ramsdell, F. (2003). An essential role for Scurfin in CD4+CD25+ T regulatory cells. Nat Immunol 4, 337-342.
Kim, D.H., Longo, M., Han, Y., Lundberg, P., Cantin, E., and Rossi, J.J. (2004). Interferon induction by siRNAs and ssRNAs synthesized by phage polymerase. Nat Biotechnol 22, 321-325.
Kinnunen, T., Jutila, K., Kwok, W.W., Rytkonen-Nissinen, M., Immonen, A., Saarelainen, S., Narvanen, A., Taivainen, A., and Virtanen, T. (2007). Potential of an altered peptide ligand of lipocalin allergen Bos d 2 for peptide immunotherapy. J Allergy Clin Immunol 119, 965-972.
Kips, J.C., O''Connor, B.J., Langley, S.J., Woodcock, A., Kerstjens, H.A., Postma, D.S., Danzig, M., Cuss, F., and Pauwels, R.A. (2003). Effect of SCH55700, a humanized anti-human interleukin-5 antibody, in severe persistent asthma: a pilot study. Am J Respir Crit Care Med 167, 1655-1659.
Kopf, M., Brombacher, F., Hodgkin, P.D., Ramsay, A.J., Milbourne, E.A., Dai, W.J., Ovington, K.S., Behm, C.A., Kohler, G., Young, I.G., and Matthaei, K.I. (1996). IL-5-deficient mice have a developmental defect in CD5+ B-1 cells and lack eosinophilia but have normal antibody and cytotoxic T cell responses. Immunity 4, 15-24.
Krug, N., Erpenbeck, V.J., Balke, K., Petschallies, J., Tschernig, T., Hohlfeld, J.M., and Fabel, H. (2001). Cytokine profile of bronchoalveolar lavage-derived CD4(+), CD8(+), and gammadelta T cells in people with asthma after segmental allergen challenge. Am J Respir Cell Mol Biol 25, 125-131.
Kung, T.T., Stelts, D.M., Zurcher, J.A., Adams, G.K., 3rd, Egan, R.W., Kreutner, W., Watnick, A.S., Jones, H., and Chapman, R.W. (1995). Involvement of IL-5 in a murine model of allergic pulmonary inflammation: prophylactic and therapeutic effect of an anti-IL-5 antibody. Am J Respir Cell Mol Biol 13, 360-365.
Kuperman, D.A., Huang, X., Koth, L.L., Chang, G.H., Dolganov, G.M., Zhu, Z., Elias, J.A., Sheppard, D., and Erle, D.J. (2002). Direct effects of interleukin-13 on epithelial cells cause airway hyperreactivity and mucus overproduction in asthma. Nat Med 8, 885-889.
Lai, W.Q., Goh, H.H., Bao, Z., Wong, W.S., Melendez, A.J., and Leung, B.P. (2008). The role of sphingosine kinase in a murine model of allergic asthma. J Immunol 180, 4323-4329.
Le Doux, J.M., Davis, H.E., Morgan, J.R., and Yarmush, M.L. (1999). Kinetics of retrovirus production and decay. Biotechnol Bioeng 63, 654-662.
Leavitt, A.D., Robles, G., Alesandro, N., and Varmus, H.E. (1996). Human immunodeficiency virus type 1 integrase mutants retain in vitro integrase activity yet fail to integrate viral DNA efficiently during infection. J Virol 70, 721-728.
Leckie, M.J., ten Brinke, A., Khan, J., Diamant, Z., O''Connor, B.J., Walls, C.M., Mathur, A.K., Cowley, H.C., Chung, K.F., Djukanovic, R., et al. (2000). Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet 356, 2144-2148.
Lee, C.C., Huang, H.Y., and Chiang, B.L. (2008). Lentiviral-mediated GATA-3 RNAi decreases allergic airway inflammation and yyperresponsiveness. Mol Ther 16, 60-65.
Lee, H.J., Koyano-Nakagawa, N., Naito, Y., Nishida, J., Arai, N., Arai, K., and Yokota, T. (1993). cAMP activates the IL-5 promoter synergistically with phorbol ester through the signaling pathway involving protein kinase A in mouse thymoma line EL-4. J Immunol 151, 6135-6142.
Lee, J.J., McGarry, M.P., Farmer, S.C., Denzler, K.L., Larson, K.A., Carrigan, P.E., Brenneise, I.E., Horton, M.A., Haczku, A., Gelfand, E.W., et al. (1997). Interleukin-5 expression in the lung epithelium of transgenic mice leads to pulmonary changes pathognomonic of asthma. J Exp Med 185, 2143-2156.
Lee, Y.L., Ye, Y.L., Yu, C.I., Wu, Y.L., Lai, Y.L., Ku, P.H., Hong, R.L., and Chiang, B.L. (2001). Construction of single-chain interleukin-12 DNA plasmid to treat airway hyperresponsiveness in an animal model of asthma. Hum Gene Ther 12, 2065-2079.
Levings, M.K., Sangregorio, R., Galbiati, F., Squadrone, S., de Waal Malefyt, R., and Roncarolo, M.G. (2001). IFN-alpha and IL-10 induce the differentiation of human type 1 T regulatory cells. J Immunol 166, 5530-5539.
Lewkowich, I.P., Herman, N.S., Schleifer, K.W., Dance, M.P., Chen, B.L., Dienger, K.M., Sproles, A.A., Shah, J.S., Kohl, J., Belkaid, Y., and Wills-Karp, M. (2005). CD4+CD25+ T cells protect against experimentally induced asthma and alter pulmonary dendritic cell phenotype and function. J Exp Med 202, 1549-1561.
Li, X.M., Schofield, B.H., Wang, Q.F., Kim, K.H., and Huang, S.K. (1998). Induction of pulmonary allergic responses by antigen-specific Th2 cells. J Immunol 160, 1378-1384.
Lilly, C.M., Nakamura, H., Kesselman, H., Nagler-Anderson, C., Asano, K., Garcia-Zepeda, E.A., Rothenberg, M.E., Drazen, J.M., and Luster, A.D. (1997). Expression of eotaxin by human lung epithelial cells: induction by cytokines and inhibition by glucocorticoids. J Clin Invest 99, 1767-1773.
Lilly, C.M., Woodruff, P.G., Camargo, C.A., Jr., Nakamura, H., Drazen, J.M., Nadel, E.S., and Hanrahan, J.P. (1999). Elevated plasma eotaxin levels in patients with acute asthma. J Allergy Clin Immunol 104, 786-790.
Lilly, C.M., Nakamura, H., Belostotsky, O.I., Haley, K.J., Garcia-Zepeda, E.A., Luster, A.D., and Israel, E. (2001). Eotaxin expression after segmental allergen challenge in subjects with atopic asthma. Am J Respir Crit Care Med 163, 1669-1675.
Lin, W., Truong, N., Grossman, W.J., Haribhai, D., Williams, C.B., Wang, J., Martin, M.G., and Chatila, T.A. (2005). Allergic dysregulation and hyperimmunoglobulinemia E in Foxp3 mutant mice. J Allergy Clin Immunol 116, 1106-1115.
Ling, E.M., Smith, T., Nguyen, X.D., Pridgeon, C., Dallman, M., Arbery, J., Carr, V.A., and Robinson, D.S. (2004). Relation of CD4+CD25+ regulatory T-cell suppression of allergen-driven T-cell activation to atopic status and expression of allergic disease. Lancet 363, 608-615.
Lopez, A.F., Begley, C.G., Williamson, D.J., Warren, D.J., Vadas, M.A., and Sanderson, C.J. (1986). Murine eosinophil differentiation factor. An eosinophil-specific colony-stimulating factor with activity for human cells. J Exp Med 163, 1085-1099.
Lopez, A.F., Sanderson, C.J., Gamble, J.R., Campbell, H.D., Young, I.G., and Vadas, M.A. (1988). Recombinant human interleukin 5 is a selective activator of human eosinophil function. J Exp Med 167, 219-224.
Main, S., Handy, R., Wilton, J., Smith, S., Williams, L., Fou, L.D., Andrews, J., Conroy, L.A., May, R., Anderson, I., and Vaughan, T.J. (2006). A potent human anti-eotaxin1 antibody, CAT-213: isolation by phage display and in vitro and in vivo efficacy. J Pharmacol Exp Ther 319, 1395-1404.
Maneechotesuwan, K., Xin, Y., Ito, K., Jazrawi, E., Lee, K.Y., Usmani, O.S., Barnes, P.J., and Adcock, I.M. (2007). Regulation of Th2 cytokine genes by p38 MAPK-mediated phosphorylation of GATA-3. J Immunol 178, 2491-2498.
Marques, J.T., and Williams, B.R. (2005). Activation of the mammalian immune system by siRNAs. Nat Biotechnol 23, 1399-1405.
McKenzie, G.J., Bancroft, A., Grencis, R.K., and McKenzie, A.N. (1998). A distinct role for interleukin-13 in Th2-cell-mediated immune responses. Curr Biol 8, 339-342.
McKenzie, G.J., Fallon, P.G., Emson, C.L., Grencis, R.K., and McKenzie, A.N. (1999). Simultaneous disruption of interleukin (IL)-4 and IL-13 defines individual roles in T helper cell type 2-mediated responses. J Exp Med 189, 1565-1572.
Montgomery, M.K., Xu, S., and Fire, A. (1998). RNA as a target of double-stranded RNA-mediated genetic interference in Caenorhabditis elegans. Proc Natl Acad Sci U S A 95, 15502-15507.
Montini, E., Cesana, D., Schmidt, M., Sanvito, F., Ponzoni, M., Bartholomae, C., Sergi Sergi, L., Benedicenti, F., Ambrosi, A., Di Serio, C., et al. (2006). Hematopoietic stem cell gene transfer in a tumor-prone mouse model uncovers low genotoxicity of lentiviral vector integration. Nat Biotechnol 24, 687-696.
Morris, K.V., Chan, S.W., Jacobsen, S.E., and Looney, D.J. (2004). Small interfering RNA-induced transcriptional gene silencing in human cells. Science 305, 1289-1292.
Morris, K.V., and Rossi, J.J. (2006). Lentivirus-mediated RNA interference therapy for human immunodeficiency virus type 1 infection. Hum Gene Ther 17, 479-486.
Nakajima, H., Sano, H., Nishimura, T., Yoshida, S., and Iwamoto, I. (1994). Role of vascular cell adhesion molecule 1/very late activation antigen 4 and intercellular adhesion molecule 1/lymphocyte function-associated antigen 1 interactions in antigen-induced eosinophil and T cell recruitment into the tissue. J Exp Med 179, 1145-1154.
Nakamura, Y., Ghaffar, O., Olivenstein, R., Taha, R.A., Soussi-Gounni, A., Zhang, D.H., Ray, A., and Hamid, Q. (1999). Gene expression of the GATA-3 transcription factor is increased in atopic asthma. J Allergy Clin Immunol 103, 215-222.
Naldini, L., Blomer, U., Gallay, P., Ory, D., Mulligan, R., Gage, F.H., Verma, I.M., and Trono, D. (1996). In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science 272, 263-267.
Ngo, H., Tschudi, C., Gull, K., and Ullu, E. (1998). Double-stranded RNA induces mRNA degradation in Trypanosoma brucei. Proc Natl Acad Sci U S A 95, 14687-14692.
Nicholson, L.B., Greer, J.M., Sobel, R.A., Lees, M.B., and Kuchroo, V.K. (1995). An altered peptide ligand mediates immune deviation and prevents autoimmune encephalomyelitis. Immunity 3, 397-405.
Nicholson, L.B., Murtaza, A., Hafler, B.P., Sette, A., and Kuchroo, V.K. (1997). A T cell receptor antagonist peptide induces T cells that mediate bystander suppression and prevent autoimmune encephalomyelitis induced with multiple myelin antigens. Proc Natl Acad Sci U S A 94, 9279-9284.
Nightingale, S.J., Hollis, R.P., Pepper, K.A., Petersen, D., Yu, X.J., Yang, C., Bahner, I., and Kohn, D.B. (2006). Transient gene expression by nonintegrating lentiviral vectors. Mol Ther 13, 1121-1132.
Nigo, Y.I., Yamashita, M., Hirahara, K., Shinnakasu, R., Inami, M., Kimura, M., Hasegawa, A., Kohno, Y., and Nakayama, T. (2006). Regulation of allergic airway inflammation through Toll-like receptor 4-mediated modification of mast cell function. Proc Natl Acad Sci U S A 103, 2286-2291.
Nouri-Aria, K.T., Wachholz, P.A., Francis, J.N., Jacobson, M.R., Walker, S.M., Wilcock, L.K., Staple, S.Q., Aalberse, R.C., Till, S.J., and Durham, S.R. (2004). Grass pollen immunotherapy induces mucosal and peripheral IL-10 responses and blocking IgG activity. J Immunol 172, 3252-3259.
O''Byrne, P., Boulet, L., Gauvreau, G., Leon, F., Sari, S., and White, B. (2007). A single dose of MEDI-528, a monoclonal antibody against interleukin-9, is well tolerated in mild and moderate asthmatics in the phase II trail MI-CP-138. Chest 132, 478S.
Paas-Rozner, M., Sela, M., and Mozes, E. (2003). A dual altered peptide ligand down-regulates myasthenogenic T cell responses by up-regulating CD25- and CTLA-4-expressing CD4+ T cells. Proc Natl Acad Sci U S A 100, 6676-6681.
Pai, S.Y., Truitt, M.L., and Ho, I.C. (2004). GATA-3 deficiency abrogates the development and maintenance of T helper type 2 cells. Proc Natl Acad Sci U S A 101, 1993-1998.
Park, C.S., Choi, Y.S., Ki, S.Y., Moon, S.H., Jeong, S.W., Uh, S.T., and Kim, Y.H. (1998). Granulocyte macrophage colony-stimulating factor is the main cytokine enhancing survival of eosinophils in asthmatic airways. Eur Respir J 12, 872-878.
Pauls, E., Senserrich, J., Bofill, M., Clotet, B., and Este, J.A. (2007). Induction of interleukins IL-6 and IL-8 by siRNA. Clin Exp Immunol 147, 189-196.
Pebernard, S., and Iggo, R.D. (2004). Determinants of interferon-stimulated gene induction by RNAi vectors. Differentiation 72, 103-111.
Pereira, S., Clark, T., Darby, Y., Salib, R., Salagean, M., Hewitt, L., Powell, J., Howarth, P., and Scadding, G. (2003). Effects of anti-eotaxin monoclonal antibody CAT-213 on allergen-induced rhinitis. J Allergy Clin Immunol 111, S268.
Philippe, S., Sarkis, C., Barkats, M., Mammeri, H., Ladroue, C., Petit, C., Mallet, J., and Serguera, C. (2006). Lentiviral vectors with a defective integrase allow efficient and sustained transgene expression in vitro and in vivo. Proc Natl Acad Sci U S A 103, 17684-17689.
Philpott, N.J., and Thrasher, A.J. (2007). Use of nonintegrating lentiviral vectors for gene therapy. Hum Gene Ther 18, 483-489.
Pope, S.M., Brandt, E.B., Mishra, A., Hogan, S.P., Zimmermann, N., Matthaei, K.I., Foster, P.S., and Rothenberg, M.E. (2001). IL-13 induces eosinophil recruitment into the lung by an IL-5- and eotaxin-dependent mechanism. J Allergy Clin Immunol 108, 594-601.
Popescu, F.D. (2005). Antisense- and RNA interference-based therapeutic strategies in allergy. J Cell Mol Med 9, 840-853.
Randolph, D.A., Carruthers, C.J., Szabo, S.J., Murphy, K.M., and Chaplin, D.D. (1999a). Modulation of airway inflammation by passive transfer of allergen-specific Th1 and Th2 cells in a mouse model of asthma. J Immunol 162, 2375-2383.
Randolph, D.A., Stephens, R., Carruthers, C.J., and Chaplin, D.D. (1999b). Cooperation between Th1 and Th2 cells in a murine model of eosinophilic airway inflammation. J Clin Invest 104, 1021-1029.
Rankin, S.M., Conroy, D.M., and Williams, T.J. (2000). Eotaxin and eosinophil recruitment: implications for human disease. Mol Med Today 6, 20-27.
Reis e Sousa, C., Levine, E.H., and Germain, R.N. (1996). Partial signaling by CD8+ T cells in response to antagonist ligands. J Exp Med 184, 149-157.
Ritprajak, P., Hashiguchi, M., and Azuma, M. (2008). Topical application of cream-emulsified CD86 siRNA ameliorates allergic skin disease by targeting cutaneous dendritic cells. Mol Ther. 16, 1323-1330.
Robbins, M., Judge, A., Liang, L., McClintock, K., Yaworski, E., and MacLachlan, I. (2007). 2''-O-methyl-modified RNAs act as TLR7 antagonists. Mol Ther 15, 1663-1669.
Robertson, J.M., Jensen, P.E., and Evavold, B.D. (2000). DO11.10 and OT-II T cells recognize a C-terminal ovalbumin 323-339 epitope. J Immunol 164, 4706-4712.
Robinson, D.S., Hamid, Q., Ying, S., Tsicopoulos, A., Barkans, J., Bentley, A.M., Corrigan, C., Durham, S.R., and Kay, A.B. (1992). Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma. N Engl J Med 326, 298-304.
Robinson, D.S., Hamid, Q., Bentley, A., Ying, S., Kay, A.B., and Durham, S.R. (1993). Activation of CD4+ T cells, increased TH2-type cytokine mRNA expression, and eosinophil recruitment in bronchoalveolar lavage after allergen inhalation challenge in patients with atopic asthma. J Allergy Clin Immunol 92, 313-324.
Robinson, D.S., Larche, M., and Durham, S.R. (2004). Tregs and allergic disease. J Clin Invest 114, 1389-1397.
Roe, T., Reynolds, T.C., Yu, G., and Brown, P.O. (1993). Integration of murine leukemia virus DNA depends on mitosis. Embo J 12, 2099-2108.
Rothenberg, M.E., Owen, W.F., Jr., Silberstein, D.S., Soberman, R.J., Austen, K.F., and Stevens, R.L. (1987). Eosinophils cocultured with endothelial cells have increased survival and functional properties. Science 237, 645-647.
Rothenberg, M.E., Pomerantz, J.L., Owen, W.F., Jr., Avraham, S., Soberman, R.J., Austen, K.F., and Stevens, R.L. (1988). Characterization of a human eosinophil proteoglycan, and augmentation of its biosynthesis and size by interleukin 3, interleukin 5, and granulocyte/macrophage colony stimulating factor. J Biol Chem 263, 13901-13908.
Rothenberg, M.E. (1998). Eosinophilia. N Engl J Med 338, 1592-1600.
Royer, B., Varadaradjalou, S., Saas, P., Guillosson, J.J., Kantelip, J.P., and Arock, M. (2001). Inhibition of IgE-induced activation of human mast cells by IL-10. Clin Exp Allergy 31, 694-704.
Rubinson, D.A., Dillon, C.P., Kwiatkowski, A.V., Sievers, C., Yang, L., Kopinja, J., Rooney, D.L., Zhang, M., Ihrig, M.M., McManus, M.T., et al. (2003). A lentivirus-based system to functionally silence genes in primary mammalian cells, stem cells and transgenic mice by RNA interference. Nat Genet 33, 401-406.
Ryan, K.R., McNeil, L.K., Dao, C., Jensen, P.E., and Evavold, B.D. (2004). Modification of peptide interaction with MHC creates TCR partial agonists. Cell Immunol 227, 70-78.
Salib, R., Salagean, M., Lau, L., DiGiovanna, I., Brennan, N., Scadding, G., and Howarthi, P. (2003). The anti-inflammatory response of anti-eotaxin monoclonal antibody CAT-213 on nasal allergen-induced cell infiltration and activation. J Allergy Clin Immunol 111, S347.
Samuel, C.E. (1993). The eIF-2 alpha protein kinases, regulators of translation in eukaryotes from yeasts to humans. J Biol Chem 268, 7603-7606.
Sanderson, C.J. (1988). Interleukin-5: an eosinophil growth and activation factor. Dev Biol Stand 69, 23-29.
Sanderson, C.J. (1992). Interleukin-5, eosinophils, and disease. Blood 79, 3101-3109.
Saxena, S., Jonsson, Z.O., and Dutta, A. (2003). Small RNAs with imperfect match to endogenous mRNA repress translation. Implications for off-target activity of small inhibitory RNA in mammalian cells. J Biol Chem 278, 44312-44319.
Schlegel, A., Schaller, J., Jentsch, P., and Kempf, C. (1993). Semliki Forest virus core protein fragmentation: its possible role in nucleocapsid disassembly. Biosci Rep 13, 333-347.
Schnyder-Candrian, S., Togbe, D., Couillin, I., Mercier, I., Brombacher, F., Quesniaux, V., Fossiez, F., Ryffel, B., and Schnyder, B. (2006). Interleukin-17 is a negative regulator of established allergic asthma. J Exp Med 203, 2715-2725.
Seder, R.A., Marth, T., Sieve, M.C., Strober, W., Letterio, J.J., Roberts, A.B., and Kelsall, B. (1998). Factors involved in the differentiation of TGF-beta-producing cells from naive CD4+ T cells: IL-4 and IFN-gamma have opposing effects, while TGF-beta positively regulates its own production. J Immunol 160, 5719-5728.
Sette, A., Buus, S., Colon, S., Smith, J.A., Miles, C., and Grey, H.M. (1987). Structural characteristics of an antigen required for its interaction with Ia and recognition by T cells. Nature 328, 395-399.
Shi, H.Z., Deng, J.M., Xu, H., Nong, Z.X., Xiao, C.Q., Liu, Z.M., Qin, S.M., Jiang, H.X., Liu, G.N., and Chen, Y.Q. (1998). Effect of inhaled interleukin-4 on airway hyperreactivity in asthmatics. Am J Respir Crit Care Med 157, 1818-1821.
Shin, D., Kim, S.I., Park, M., and Kim, M. (2007). Immunostimulatory properties and antiviral activity of modified HBV-specific siRNAs. Biochem Biophys Res Commun 364, 436-442.
Sioud, M. (2006). Single-stranded small interfering RNA are more immunostimulatory than their double-stranded counterparts: a central role for 2''-hydroxyl uridines in immune responses. Eur J Immunol 36, 1222-1230.
Sioud, M., Furset, G., and Cekaite, L. (2007). Suppression of immunostimulatory siRNA-driven innate immune activation by 2''-modified RNAs. Biochem Biophys Res Commun 361, 122-126.
Sledz, C.A., Holko, M., de Veer, M.J., Silverman, R.H., and Williams, B.R. (2003). Activation of the interferon system by short-interfering RNAs. Nat Cell Biol 5, 834-839.
Sloan-Lancaster, J., Evavold, B.D., and Allen, P.M. (1993). Induction of T-cell anergy by altered T-cell-receptor ligand on live antigen-presenting cells. Nature 363, 156-159.
Sloan-Lancaster, J., Shaw, A.S., Rothbard, J.B., and Allen, P.M. (1994). Partial T cell signaling: altered phospho-zeta and lack of zap70 recruitment in APL-induced T cell anergy. Cell 79, 913-922.
Sloan-Lancaster, J., and Allen, P.M. (1996). Altered peptide ligand-induced partial T cell activation: molecular mechanisms and role in T cell biology. Annu Rev Immunol 14, 1-27.
Stewart, S.A., Dykxhoorn, D.M., Palliser, D., Mizuno, H., Yu, E.Y., An, D.S., Sabatini, D.M., Chen, I.S., Hahn, W.C., Sharp, P.A., et al. (2003). Lentivirus-delivered stable gene silencing by RNAi in primary cells. Rna 9, 493-501.
Strachan, D.P. (1989). Hay fever, hygiene, and household size. Brit. Med. J. 299, 1259-1260.
Strickland, D.H., Stumbles, P.A., Zosky, G.R., Subrata, L.S., Thomas, J.A., Turner, D.J., Sly, P.D., and Holt, P.G. (2006). Reversal of airway hyperresponsiveness by induction of airway mucosal CD4+CD25+ regulatory T cells. J Exp Med 203, 2649-2660.
Strunk, R.C., and Bloomberg, G.R. (2006). Omalizumab for asthma. N Engl J Med 354, 2689-2695.
Sumimoto, H., and Kawakami, Y. (2007). Lentiviral vector-mediated RNAi and its use for cancer research. Future Oncol 3, 655-664.
Suto, A., Nakajima, H., Kagami, S.I., Suzuki, K., Saito, Y., and Iwamoto, I. (2001). Role of CD4(+) CD25(+) regulatory T cells in T helper 2 cell-mediated allergic inflammation in the airways. Am J Respir Crit Care Med 164, 680-687.
Takanaski, S., Nonaka, R., Xing, Z., O''Byrne, P., Dolovich, J., and Jordana, M. (1994). Interleukin 10 inhibits lipopolysaccharide-induced survival and cytokine production by human peripheral blood eosinophils. J Exp Med 180, 711-715.
Tan, W., Dong, Z., Wilkinson, T.A., Barbas, C.F., 3rd, and Chow, S.A. (2006). Human immunodeficiency virus type 1 incorporated with fusion proteins consisting of integrase and the designed polydactyl zinc finger protein E2C can bias integration of viral DNA into a predetermined chromosomal region in human cells. J Virol 80, 1939-1948.
Teran, L.M., Mochizuki, M., Bartels, J., Valencia, E.L., Nakajima, T., Hirai, K., and Schroder, J.M. (1999). Th1- and Th2-type cytokines regulate the expression and production of eotaxin and RANTES by human lung fibroblasts. Am J Respir Cell Mol Biol 20, 777-786.
Terskikh, A.V., Ershler, M.A., Drize, N.J., Nifontova, I.N., and Chertkov, J.L. (2005). Long-term persistence of a nonintegrated lentiviral vector in mouse hematopoietic stem cells. Exp Hematol 33, 873-882.
Till, S., Li, B., Durham, S., Humbert, M., Assoufi, B., Huston, D., Dickason, R., Jeannin, P., Kay, A.B., and Corrigan, C. (1995). Secretion of the eosinophil-active cytokines interleukin-5, granulocyte/macrophage colony-stimulating factor and interleukin-3 by bronchoalveolar lavage CD4+ and CD8+ T cell lines in atopic asthmatics, and atopic and non-atopic controls. Eur J Immunol 25, 2727-2731.
Trian, T., Girodet, P.O., Ousova, O., Marthan, R., Tunon-de-Lara, J.M., and Berger, P. (2006). RNA interference decreases PAR-2 expression and function in human airway smooth muscle cells. Am J Respir Cell Mol Biol 34, 49-55.
Tsitoura, D.C., Holter, W., Cerwenka, A., Gelder, C.M., and Lamb, J.R. (1996). Induction of anergy in human T helper 0 cells by stimulation with altered T cell antigen receptor ligands. J Immunol 156, 2801-2808.
Usui, T., Nishikomori, R., Kitani, A., and Strober, W. (2003). GATA-3 suppresses Th1 development by downregulation of Stat4 and not through effects on IL-12Rbeta2 chain or T-bet. Immunity 18, 415-428.
Usui, T., Preiss, J.C., Kanno, Y., Yao, Z.J., Bream, J.H., O''Shea, J.J., and Strober, W. (2006). T-bet regulates Th1 responses through essential effects on GATA-3 function rather than on IFNG gene acetylation and transcription. J Exp Med 203, 755-766.
Vercelli, D. (2008). Discovering susceptibility genes for asthma and allergy. Nat Rev Immunol 8, 169-182.
Walker, C., Virchow, J.C., Jr., Bruijnzeel, P.L., and Blaser, K. (1991). T cell subsets and their soluble products regulate eosinophilia in allergic and nonallergic asthma. J Immunol 146, 1829-1835.
Walker, C., Bode, E., Boer, L., Hansel, T.T., Blaser, K., and Virchow, J.C., Jr. (1992). Allergic and nonallergic asthmatics have distinct patterns of T-cell activation and cytokine production in peripheral blood and bronchoalveolar lavage. Am Rev Respir Dis 146, 109-115.
Walter, D.M., McIntire, J.J., Berry, G., McKenzie, A.N., Donaldson, D.D., DeKruyff, R.H., and Umetsu, D.T. (2001). Critical role for IL-13 in the development of allergen-induced airway hyperreactivity. J Immunol 167, 4668-4675.
Wang, J.M., Rambaldi, A., Biondi, A., Chen, Z.G., Sanderson, C.J., and Mantovani, A. (1989). Recombinant human interleukin 5 is a selective eosinophil chemoattractant. Eur J Immunol 19, 701-705.
Wang, L.C., Lee, J.H., Yang, Y.H., Lin, Y.T., and Chiang, B.L. (2007). New biological approaches in asthma: DNA-based therapy. Curr Med Chem 14, 1607-1618.
Wang, X., Xu, W., Mohapatra, S., Kong, X., Li, X., Lockey, R.F., and Mohapatra, S.S. (2008). Prevention of airway inflammation with topical cream containing imiquimod and small interfering RNA for natriuretic peptide receptor. Genet Vaccines Ther 6, 7.
Wiktor-Jedrzejczak, W. (1993). Eosinophil development. Immunol Today 14, 238.
Wills-Karp, M., Luyimbazi, J., Xu, X., Schofield, B., Neben, T.Y., Karp, C.L., and Donaldson, D.D. (1998). Interleukin-13: central mediator of allergic asthma. Science 282, 2258-2261.
Windhagen, A., Scholz, C., Hollsberg, P., Fukaura, H., Sette, A., and Hafler, D.A. (1995). Modulation of cytokine patterns of human autoreactive T cell clones by a single amino acid substitution of their peptide ligand. Immunity 2, 373-380.
Wynn, T.A. (2003). IL-13 effector functions. Annu Rev Immunol 21, 425-456.
Yamaguchi, Y., Suda, T., Suda, J., Eguchi, M., Miura, Y., Harada, N., Tominaga, A., and Takatsu, K. (1988). Purified interleukin 5 supports the terminal differentiation and proliferation of murine eosinophilic precursors. J Exp Med 167, 43-56.
Yanez-Munoz, R.J., Balaggan, K.S., MacNeil, A., Howe, S.J., Schmidt, M., Smith, A.J., Buch, P., MacLaren, R.E., Anderson, P.N., Barker, S.E., et al. (2006). Effective gene therapy with nonintegrating lentiviral vectors. Nat Med 12, 348-353.
Ying, S., Meng, Q., Zeibecoglou, K., Robinson, D.S., Macfarlane, A., Humbert, M., and Kay, A.B. (1999). Eosinophil chemotactic chemokines (eotaxin, eotaxin-2, RANTES, monocyte chemoattractant protein-3 (MCP-3), and MCP-4), and C-C chemokine receptor 3 expression in bronchial biopsies from atopic and nonatopic (Intrinsic) asthmatics. J Immunol 163, 6321-6329.
Young, D.A., Lowe, L.D., Booth, S.S., Whitters, M.J., Nicholson, L., Kuchroo, V.K., and Collins, M. (2000). IL-4, IL-10, IL-13, and TGF-beta from an altered peptide ligand-specific Th2 cell clone down-regulate adoptive transfer of experimental autoimmune encephalomyelitis. J Immunol 164, 3563-3572.
Yuan, Q., Campanella, G.S., Colvin, R.A., Hamilos, D.L., Jones, K.J., Mathew, A., Means, T.K., and Luster, A.D. (2006). Membrane-bound eotaxin-3 mediates eosinophil transepithelial migration in IL-4-stimulated epithelial cells. Eur J Immunol 36, 2700-2714.
Zhang, D.H., Yang, L., Cohn, L., Parkyn, L., Homer, R., Ray, P., and Ray, A. (1999). Inhibition of allergic inflammation in a murine model of asthma by expression of a dominant-negative mutant of GATA-3. Immunity 11, 473-482.
Zhu, J., Min, B., Hu-Li, J., Watson, C.J., Grinberg, A., Wang, Q., Killeen, N., Urban, J.F., Jr., Guo, L., and Paul, W.E. (2004). Conditional deletion of Gata3 shows its essential function in T(H)1-T(H)2 responses. Nat Immunol 5, 1157-1165.
Zhu, Z., Homer, R.J., Wang, Z., Chen, Q., Geba, G.P., Wang, J., Zhang, Y., and Elias, J.A. (1999). Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production. J Clin Invest 103, 779-788.
Zimmermann, N., Hershey, G.K., Foster, P.S., and Rothenberg, M.E. (2003). Chemokines in asthma: cooperative interaction between chemokines and IL-13. J Allergy Clin Immunol 111, 227-242; quiz 243.
Zufferey, R., Nagy, D., Mandel, R.J., Naldini, L., and Trono, D. (1997). Multiply attenuated lentiviral vector achieves efficient gene delivery in vivo. Nat Biotechnol 15, 871-875.
Zufferey, R., Dull, T., Mandel, R.J., Bukovsky, A., Quiroz, D., Naldini, L., and Trono, D. (1998). Self-inactivating lentivirus vector for safe and efficient in vivo gene delivery. J Virol 72, 9873-9880.
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