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研究生:孫昭玲
研究生(外文):Suen Jau-Ling
論文名稱:骨髓樹突細胞應用在全身性紅斑狼瘡動物模式snRNP-U1A自體免疫反應的探討
論文名稱(外文):Study on self-reactive immune response to snRNP-U1A protein with bone marrow-derived dendritic cell in murine lupus
指導教授:江伯倫江伯倫引用關係
指導教授(外文):Chiang Bor-Luen
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:2001
畢業學年度:89
語文別:英文
論文頁數:172
中文關鍵詞:骨髓樹突細胞全身性紅斑狼瘡自體免疫
外文關鍵詞:bone marrow-derived dendrtic cellsystemic lupus erythematosusautoimmunesnRNP-U1A
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全身性紅斑狼瘡(systemic lupus erythematosus; SLE)的特徵是具有多種的自體抗體,而這些抗體主要是辨識細胞核內的完整結構,例如:nucleosome或是small nuclear ribonucleoprotein(snRNP),其中抗snRNP抗體主要可在全身性紅斑狼瘡,或混合性結締組織病(mixed connected tissue disease; MCTD)病人的血清中測得;而U1A蛋白質是U1 snRNP結構中,引起免疫反應的主要抗原,且在小鼠模式MRL-lpr/lpr中證實,透過分子間或是結構內的免疫反應,可使針對U1A的免疫反應擴展(spreading)到其他snRNP中的組成蛋白;然而有關snRNP的T細胞抗原決定位(T cell epitopes)及snRNP如何擴展免疫反應到其他結構內的組成分子(intrastructural spreading)之相關研究報告仍然很少。本論文的研究著重在兩方面,一是利用骨髓樹突細胞(bone marrow-derived dendritic cell; BM-DC)來鑑定全身性紅斑狼瘡小鼠模式中U1A的T細胞抗原決定位;另一方面,在正常小鼠體內注射可呈獻U1A的骨髓樹突細胞,藉以檢測此處理是否可打破自體耐受性(self-tolerance breakdown),進而引發自體免疫疾病。
根據以前的研究顯示,以B細胞或是巨噬細胞(macrophage)當作抗原呈獻細胞,並不容易直接檢測出T細胞抗原決定位,但是在本實驗中,在全身性紅斑狼瘡小鼠模式下,利用骨髓樹突細胞卻可以直接鑑定出U1A蛋白質的T細胞抗原決定位;就我們所知,這是第一個在BWF1小鼠模式中,有關U1A之T細胞抗原決定位的報導;這T細胞抗原決定位位於小鼠U1A蛋白質的C端,和全身性紅斑狼瘡病人的U1A之T細胞抗原決定位的胺基酸序列重疊。鑑定snRNP的T細胞抗原決定位可以幫助了解在全身性紅斑狼瘡病人體內,snRNP如何擴展免疫反應到結構內的組成分子;另一方面,用樹突細胞鑑定自體抗原T細胞抗原決定位可以更進一步應用在全身性紅斑狼瘡的免疫治療。
樹突細胞可以引發及掌控針對外來抗原的免疫反應。越來越多的證據顯示自體免疫反應也可以由樹突細胞所引發,為了更進一步了解骨髓樹突細胞在引發自體免疫反應上所扮演的角色,將呈獻U1A蛋白質的骨髓樹突細胞直接由靜脈注射入正常小鼠(BALB/c或DBA/NZW F1)體內,發現可以活化自體反應T細胞並引發產生高效價的抗U1A之IgG抗體,這些具有抗U1A免疫反應的小鼠,可過渡性的產生抗DNA的IgG抗體,但是並不像全身性紅斑狼瘡小鼠模式(BWF1)一樣,會發生腎臟病變。而且在經過十個月的追蹤後,可以發現有IgG抗體沉積其上,但是卻無補體C3蛋白的沉積;另外,DBA/NZW F1小鼠體內的U1A-specific T細胞產生的細胞激素與BWF1小鼠的比起來較偏向第一型輔助性T細胞(Th1)。
由研究結果顯示,我們的動物模式未來可以應用在探討全身性紅斑狼瘡epitope spreading的自體反應致病機轉,而且可以找出負責幫忙抗DNA抗體產生的T細胞為何,進而建立其動物模式,探討疾病發生機制。

Systemic lupus erythematosus (SLE) is characterized by the existence of a heterogeneous group of autoantibodies directed against nuclear intact structures, such as nucleosomes and small nuclear ribonucleoproteins (snRNPs). Autoantibodies against snRNPs are of special interest since they are detectable in a majority of SLE and mixed connected tissue disease (MCTD) patients. In addition, U1A is the immunodominant antigen (Ag) of U1 snRNP and epitope spread to other components of self U snRNPs through intermolecular/intrastructural help in MRL-lpr/lpr mice. However, very limited data about the T cell epitopes of snRNPs and how the epitope spreads to other components of snRNP have been reported. The major aim of this study is to determine the auto-T cell epitopes in murine lupus using bone marrow-derived dendritic cells (BM-DCs) pulsed with the murine U1A protein and to investigate whether BM-DCs pulsed with U1A can break the tolerance in normal mice in vivo and eventually induce an autoimmune disease.
Several studies have demonstrated that determination of the auto-T cell epitopes recognized by freshly isolated T cells is difficult from unprimed lupus mice when self-antigen pulsed-B cells or macrophages are used as antigen presenting cells (APCs) in vitro. However, in the present study, BM-DCs pulsed with the murine U1A protein were able to process and present auto-T cell epitopes to activate freshly isolated T cells from unprimed (NZB × NZW) F1 (BWF1) mice in vitro. This is, to our knowledge, the first report to demonstrate the existence of an anti-U1A IgG and U1A-specific CD4+ T cell in BWF1 mice. The T cell epitope area was found to be located at the C-terminus of U1A, overlapping the T cell epitope of human U1A that has been reported in human SLE. Identification of the autoreactive T cell epitope(s) in snRNPs will help in understanding how reciprocal T-B determinant spreading of snRNPs emerges in lupus. The results presented here also indicate that it is feasible to use this approach to further explore strategies to design immunotherapy in lupus.
Immune responses against foreign Ags are initiated and controlled by dendritic cells. Accumulating evidences suggest that autoimmunity can also be primed by dendritic cells. To further determine the role of BM-DCs in the initiation of autoimmunity and, the question of whether BM-DCs pulsed with self-antigen can break the tolerance in normal mice in vivo and eventually induce an autoimmune disease was investigated. The results showed that BM-DCs pulsed with U1A proteins by intravenous injection into BALB/c (H-2d) and DBA-2 × NZW F1 (H-2d/u) mice were capable of eliciting activation of autoreactive T cells and inducing a high titer of IgG anti-U1A antibody (Ab). Both BALB/c and DBA-2 × NZW F1 mice with a high titer of anti-U1A autoantibody also transiently develop IgG against double-stranded (ds) and single-stranded (ss) DNA. However, unlike BWF1 (H-2d/u) mice, no obviously histopathological changes to the glomeruli were noted in BM-DCs or in U1A-pulsed BM-DCs-immunized animals. Interestingly, all U1A-pulsed BM-DCs treated mice did develop IgG, but not complement C3 deposition in the glomeruli several months after immunization. In addition, the cytokine profile produced by U1A-specific T cells of primed DBA-2 × NZW F1 mice was toward the Th1 phenotype compared with that of BWF1 mice. The data here suggests that several factors, such as cytokine environment or genetic background, influence the propagation of the autoimmune response.
Taken together, the model here helps further understanding of the pathogenic mechanisms such as self-antigens shifting and autoreactive T cells development in murine lupus. In addition, the information derived from these experiments might lead to the identification of the T cell epitope(s) responsible for the anti-DNA IgG production and create a self-antigen specific experimental model for the dissection of the mechanisms by which autoimmunity develops.

標題……………………………………………………………………………...i
口試委員會審定書……………………………………………………………...ii
授權書…………………………………………………………………………...iii
誌謝……………………………………………………………………………...v
中文摘要…………………………………………………………….…………..vi
ABSTRACT……………………………………………………..……………….viii
ABBREVIATION………………………………………………………………..xi
CONTENTS……………………………………………………………………...xiv
CHAPTER I. General Introduction…………………………………………...1
1.1 An overview of the pathogenesis of systemic lupus erythematosus………………………………………………………..2
1.1.1 Genetic susceptibility…………………………….………….2
1.1.2 Environmental triggers………………………………………3
1.1.3 The involvement of sex hormone……………………………4
1.1.4 Neuroendocrine system……………………………………...4
1.1.5 B cell abnormalities………………………………………….4
1.1.6 T cell involvement……………………………………….…..6
1.1.7 The mediators of tissue damage………………….………….8
1.2 The murine model of SLE - NZB × NZW F1 mice………………...9
1.3 The epitope spreading
1.3.1The concept of epitope spreading……………………………..10
1.3.2The epitope spreading in SLE…………………………………11
1.3.3T-B cell interaction……………………………………………12
1.4 Bone marrow-derived dendritic cell………………………………..13
1.4.1The life cycle of dendritic cell…………………….…………..13
1.4.2The subsets of dendritic cells………………………………….14
1.4.3The role of dendritic cells in vitro and in vivo………………..15
1.4.4DC in cancer therapy………………………………………….16
1.4.5The role of dendritic cell in autoimmunity……………………17
1.5 Aims of the study……………………………………………………..19
CHAPTER II. Preparation of self-antigen — snRNP U1A…………………...22
2.1 Introduction…………………………………………………………...23
2.2 Materials and Methods………………………………………………..24
2.3 Results………………………………………………………………….25
2.4 Discussion………………………………………………….…………..26
CHAPTER III. Characterization of the antigenic presenting ability of
BM-DCs in vitro and in vivo…………………………….……27
3.1 Introduction…………………………………………………………...28
3.2 Materials and Methods……………………………………………….28
3.3 Results…………………………………………………………………32
3.4 Discussion………………………………………………….…………..33
CHAPTER IV. Characterization of self-T cell response and antigenic determinants of U1A protein with BM-DCs in BWF1 mice……………………………………………………………36
4.1 Introduction……………………………………………………………37
4.2 Materials and Methods…………………………………….…………38
4.3 Results…………………………………………………………………43
4.4 Discussion……………………………………………………………...49
CHAPTER V. In vivo tolerance breakdown with dendritic cells pulsed
with U1A protein in nonautoimmune mice: Induction of
a high level of autoantibody but not renal pathological
changes…………………………………………………………54
5.1 Introduction……………………………………………………………55
5.2 Materials and Methods…………………………………….………….56
5.3 Results………………………………………………………………….60
5.4 Discussion………………………………………………….…………..64
CHAPTER VI. Conclusion and Perspectives…………………………………69
6.1 Conclusion……………………………………………………………..70
6.2 Perspectives……………………………………………………………72
Tables……………………………………………………………………………75
Figures…………………………………………………………………………..81
Reference………………………………………………………………………..118
Appendices………………………………………………………………………135
Appendix I: Commonly used reagents……………………………………..136
Appendix II: Experiment procedures………………………………………139
Accompanying paper with the thesis………………………………………164

Albert, M.L., Sauter, B., and Bhardwaj, N. (1998). Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs. Nature 392, 86-89.
Alderuccio, F., Toh, B.H., Tan, S.S., Gleeson, P.A., and van Driel, I.R. (1993). An autoimmune disease with multiple molecular targets abrogated by the transgenic expression of a single autoantigen in the thymus. J. Exp. Med. 178, 419-426.
Amoura, Z., Piette, J.C., Chabre, H., Cacoub, P., Papo, T., Wechsler, B., Bach, J.F., and Koutouzov, S. (1997). Circulating plasma levels of nucleosomes in patients with systemic lupus erythematosus — Correlation with serum antinucleosome antibody titers and absence of clear association with disease activity. Arthritis Rheum. 40, 2217-2225.
Andrews, B.S., Eisenberg, R.A., Theofilopoulos, A.N., Izui, S., Wilson, C.B., McConahey, P.J., Murphy, E.D., Roths, J.B., and Dixon, F.J. (1978). Spontaneous murine lupus-like syndromes. Clinical and immuno- pathological manifestations in several strains. J. Exp. Med. 148, 1198-1215.
Bach, J.F., Koutouzov, S., and van Endert, P.M. (1998). Are there unique autoantigens triggering autoimmune diseases? Immunol. Rev. 164, 139-155.
Banchereau, J., and Steinman, R.M. (1998). Dendritic cells and the control of immunity. Nature 392, 245-252.
Banchereau, J., Briere, F., Caux, C., Davoust, J., Lebecque, S., Liu, Y.J., Pulendran, B., and Palucka, K. (2000). Immunobiology of dendritic cells. Annu. Rev. Immunol. 18, 767-811.
Bell, D., Young, J.W., and Banchereau, J. (1999). Dendritic cells. Adv. Immunol. 72, 255-324.
Bennett, M.M., Baron, M.A., and Craft, J. (1993). Nucleotide sequence analysis of the A protein of the U1 small nuclear ribonucleoprotein particle: the murine protein contains a 5’ amino-terminal tag. Nucleic Acid Res. 21, 4404.
Berden, J.H.M., Licht, R., van Bruggen, M.C.J., and Tax, W.J.M. (1999). Role of nucleosomes for induction and glomerular binding of autoantibodies in lupus nephritis. Curr. Opin. Nephrol. Hypertens. 8, 299-306.
Bhardwaj, N., Young, J.W., Nisanian, A.J., Baggers, J., and Steinman, R.M. (1993). Small amounts of superantigen, when presented on dendritic cells, are sufficient to initiate T cell responses. J. Exp. Med. 178, 633-642.
Bickerstaff, M.C., Botto, M., Hutchinson, W.L., Herbert, J., Tennent, G.A., Bybee, A., Mitchell, D.A., Cook, H.T., Butler, P.J., Walport, M.J., and Pepys, M.B. (1999). Serum amyloid P component controls chromatin degradation and prevents antinuclear autoimmunity. Nat. Med. 5, 694-697.
Binks, M., Jones, G.E., Brickell, P.M., Kinnon, C., Katz, D.R., and Thrasher, A.J. (1998). Intrinsic dendritic cell abnormalities in Wiscott-Aldrich syndrome. Eur. J. Immunol. 28, 3259-3267.
Bockenstedt, L.K., Gee, R.J., and Mamula, M.J. (1995). Self peptides in the initiation of lupus autoimmunity. J. Immunol. 154, 3516-3524.
Botto, M., Dell'Agnola, C., Bygrave, A.E., Thompson, E.M., Cook, H.T., Petry, F., Loos, M., Pandolfi, P.P., and Walport, M.J. (1998). Homozygous C1q deficiency causes glomerulonephritis associated with multiple apoptotic bodies. Nat. Genet. 19, 56-59.
Boumpas, D.T., Austin, H.A.I., Fessler, B.J., Balow, J.E., Klippel, J.H., and Lockshin, M.D. (1995a). Systemic lupus erythematosus: emerging concepts. Part 1: Renal, neuropsychiatric, cardiovascular, pulmonary, and hematologic disease. Ann. Intern. Med. 122, 940-950.
Boumpas, D.T., Fessler, B.J., Austin, H.A.I., Balow, J.E., Klippel, J.H., and Lockshin, M.D. (1995b). Systemic lupus erythematosus: emerging concepts. Part 2: Dermatologic and joint disease, the anti-phospholipid antibody syndrome, pregnancy and hormonal therapy, morbidity and mortality, and pathogenesis. Ann. Intern. Med. 123, 42-53.
Burlingame, R.W., and Rubin, R.L. (1990). Subnucleosome structures as substrates in enzyme-linked immunosorbent assays. J. Immunol. Methods 134, 187-199.
Butz, E.A., and Bevan, M.J. (1998). Differential presentation of the same MHC class I epitopes by fibroblasts and dendritic cells. J. Immunol. 160, 2139-2144.
Casciola-Rosen, L.A., Anhalt, G., and Rosen, A. (1994). Autoantigens targeted in systemic lupus erythematosus are clustered in two populations of surface structures on apoptotic keratinocytes. J. Exp. Med. 179, 1317-1330.
Caux, C., Vanbervliet, B., Massacrier, C., Azuma, M., Okumura, K., Lanier, L.L., and Banchereau, J. (1994). B70/B7.2 is identical to CD86 and is the major functional ligand for CD28 expressed on human dendritic cells. J. Exp. Med. 180, 1841-1847.
Cawley, D., Chiang, B.L., Naiki, M., Ansari, A.A., and Gershwin, M.E. (1993). Comparison of the requirements for cognate T cell help for IgG anti-double-stranded DNA antibody production in vitro: T helper-derived lymphokines replace T cell cloned lines for B cells from NZB.H-2bm12 but not B6.H-2 bm12 mice. J. Immunol. 150, 2467-2477.
Chan, O., and Shlomchik, M.J. (1998). A New role for B cells in systemic autoimmunity: B cells promote spontaneous T cell activation in MRL-lpr/lpr mice. J. Immunol. 160, 51-59.
Chen, Y.C., Ye, Y.L., and Chiang, B.L. (1997). Establishment and characterization of cloned CD4- CD8- ab-T cell receptor (TCR)-bearing autoreactive T cells from autoimmune NZB × NZW F1 mice. Clin. Exp. Immunol. 108, 52-57.
Dean, G.S., Tyrrell-Price, J., Crawley, E., and Isenberg, D.A. (2000). Cytokines and systemic lupus erythematosus. Ann. Rheum. Dis. 59, 243-251.
Dittel, B.N., Visintin, I., Merchant, R.M., and Janeway, C.A. Jr. (1999). Presentation of the self antigen myelin basic protein by dendritic cells leads to experimental autoimmune encephalomyelitis. J. Immunol. 163, 32-39.
Drake, C.G., Rozzo, S.J., Vyse, T.J., Palmer, E., and Kotzin, B.L. (1995). Genetic contributions to lupus-like disease in (NZB×NZW) F1 mice. Immunol. Rev. 144, 51-74.
Ebling, F.M., Tsao, B.P., Singh, R.R., Sercarz, E., and Hahn, B.H. (1993). A peptide derived from an autoantibody can stimulate T cells in the (NZB × NZW) F1 mouse model of systemic lupus erythematosus. Arthritis Rheum. 36, 355-364.
Fatenejad, S., and Craft, J. (1996). Intrastructural help in diversification of humoral autoimmune responses. Clin. Exp. Immunol. 106, 1-4.
Fatenejad, S., Bennett, M., Moslehi, J., and Craft, J. (1998). Influence of antigen organization on the development of lupus autoantibodies. Arthritis Rheum. 41, 603-612.
Fatenejad, S., Brooks, W., Schwartz, A., and Craft, J. (1994). Pattern of anti-small nuclear ribonucleoprotein antibodies in MRL/Mp-lpr/lpr mice suggests that the intact U1 snRNP particle is their autoimmunogenic target. J. Immunol. 152, 5523-5531.
Fatenejad, S., Mamula, M.J., and Craft, J. (1993). Role of intermolecular / intrastructural B- and T-cell determinants in the diversification of autoantibodies to ribonucleoproteins particles. Proc. Natl. Acad. Sci. USA 90, 12010-12014.
Finck, B.K., Linsley, P.S., and Wofsy, D. (1994). Treatment of murine lupus with CTLA4 Ig. Science 265, 1225-1227.
Flores-Romo, L. (2001). In vivo maturation and migration of dendritic cells. Immunology 102, 255-262.
Fong, L., and Engleman, E.G. (2000). Dendritic cells in cancer immunotherapy. Ann. Reviews 18, 245-273.
Foster, M.H., and Kelley, V.R. (1999). Lupus nephritis: update on pathogenesis and disease mechanisms. Semin. Nephrol. 19, 173-181.
Foster, M.H., Cizman, B., and Madaio, M.P. (1993). Nephritogenic autoantibodies in systemic lupus erythematosus: immunochemical properties, mechanisms of immune deposition, and genetic origins. Lab. Invest. 69, 494-507.
Gallucci, S., Lolkema, M., and Matzinger, P. (1999). Natural adjuvants: endogenous activators of dendritic cells. Nat. Med. 5, 1249-1255.
Geiger, T., Gooding, L.R., and Flavell, R.A. (1992). T-cell responsiveness to an oncogenic peripheral protein and spontaneous autoimmunity in transgenic mice. Proc. Natl. Acad. Sci. USA 89, 2985-2989.
Hahn, B.H. (1998). Antibodies to DNA. N. Engl. J. Med. 338, 1359-1367.
Hardin, J.A. (1986). The lupus autoantigens and the pathogenesis of systemic lupus erythematosus. Arthritis Rheum. 29, 457-460.
Herrmann, M., Voll, R.E., and Kalden, J.R. (2000). Etiopathogenesis of systemic lupus erythematosus. Immunol. Today 21, 424-426.
Herrmann, M., Voll, R.E., Zoller, O.M., Hagenhofer, M., Ponner, B.B., and Kalden, J.R. (1998). Impaired phagocytosis of apoptotic cell material by monocyte-derived macrophages from patients with systemic lupus erythematosus. Arthritis Rheum. 41, 1241-1250.
Inaba, K., Inaba, M., Naito, M., and Steinman, R.M. (1993). Dendritic cell progenitors phagocytose particulates, including Bacillus Calmette-Guerin organisms, and sensitize mice to mycobacterial antigens in vivo. J. Exp. Med. 178, 479-488.
Inaba, K., Inaba, M., Romani, N., Aya, H., Deguchi, M., Ikehara, S., Muramatsu, S., and Steinman, R.M. (1992). Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte / macrophage colony-stimulating factor. J. Exp. Med. 176, 1693-1702.
Inaba, K., Metlay, J.P., Crowley, M.T., and Steinman, R.M. (1990). Dendritic cells pulsed with protein antigens in vitro can prime antigen-specific, MHC-restricted T cells in situ. J. Exp. Med. 172, 631-640.
Inaba, K., Pack, M., Inaba, M., Sakuta, H., Isdell, F., and Steinman, R.M. (1997). High levels of a major histocompatibility complex II-self peptide complex on dendritic cells from lymph node. J. Exp. Med. 186, 665-672.
Inaba, K., Witmer-Pack, M., Inaba, M., Hathcock, K.S., Sakuta, H., Azuma, M., Yagita, H., Okumura, K., Linsley, P.S., Ikehara, S., et al. (1994). The tissue distribution of the B7.2 costimulator in mice: abundant expression on dendritic cells in situ and during maturation in vitro. J. Exp. Med. 180, 1849-1860.
Ingulli, E., Mondino, A., Khoruts, A., and Jenkins, M.K. (1997). In vivo detection of dendritic cell antigen presentation to CD4+ T cells. J. Exp. Med. 185, 2133-2241.
Kaliyaperumal, A., Michaels, M.A., and Datta, S.K. (1999). Antigen- specific therapy of murine lupus nephritis using nucleosomal peptides: tolerance spreading impairs pathogenic function of autoimmune T and B cells. J. Immunol. 162, 5775-5783.
Kaliyaperumal, A., Mohan, C., Wu, W., and Datta, S.K. (1996). Nucleosomal peptide epitopes for nephritis-inducing T helper cells of murine lupus. J. Exp. Med. 183, 2459-2469.
Kanno, k., Okada, T., Abe, M., Hirose, S., and Shirai, T. (1993). Differential sensitivity to interleukins of CD5+ and CD5- anti-DNA antibody-producing B cells in murine lupus. Autoimmunity 14, 205-214.
Kaufman, D.L., Clare-Salzler, M., Tian, J., Forsthuber, T., Ting, G.S., Robinson, P., Atkinson, M.A., Sercarz, E.E., Tobin, A.J., and Lehmann, P.V. (1993). Spontaneous loss of T-cell tolerance to glutamic acid decarboxylase in murine insulin-dependent diabetes. Nature 366, 69-72.
Kawahata, K., Misaki, Y., Komagata, Y., Setoguchi, K., Tsunekawa, S., Yoshikawa, Y., Miyazaki, J., and Yamamoto, K. (1999). Altered expression level of a systemic nuclear autoantigen determines the fate of immune response to self. J. Immunol. 162, 6482-6491.
Kotzin, B.L. (1996). Systemic lupus erythematosus. Cell 85, 303-306.
Kotzin, B.L., and O’Dell, J.R. (1995). Systemic lupus erythematosus. In Samter’s Immunologic Diseases, Fifth Edition, M.M. Frank, K.F. Austen, H.N. Claman, and E.R. Unanue, eds. (Boston: Little, Brown & Co.). pp 667-697.
Kudo, S., Matsuno, K., Ezaki, T., and Ogawa, M. (1997). A novel migration pathway for rat dendritic cells from the blood: Hepatic sinusoids-lymph translocation. J. Exp. Med. 185, 777-784.
Lehmann, P.V., Forsthuber, T., Miller, A., and Sercarz, E.E. (1992). Spreading of T-cell autoimmunity to cryptic determinants of an autoantigen. Nature 359, 155-157.
Liblau, R., Tisch, R., Bercovici, N., and McDevitt, H.O. (1997). Systemic antigen in the treatment of T-cell-mediated autoimmune diseases. Immunol. Today 18, 599-604.
Lin, B.F., Huang, C.C., Chiang, B.L., and Jeng, S.J. (1996). Effects of fat nutrition on Ia antigen expression, prostaglandin E2 and cytokines production in autoimmune prone NZB × NZW F1 mice. Br. J. Nutr. 75, 711-722.
Lin, L.C., Chen, Y.C., Chou, C.C., Hsieh, K.H., and Chiang, B.L. (1995). Dysregulation of T helper cell cytokines in autoimmune prone NZB × NZW F1 mice. Scand. J. Immunol. 42, 466-472.
Lu, L., Kaliyaperumal, A., Boumpas, D.T., and Datta, S.K. (1999). Major peptide autoepitopes for nucleosome-specific T cells of human lupus. J. Clin. Invest. 104, 345-355.
Ludewig, B., Odermatt, B., Landmann, S., Hengartner, H., and Zinkernagel, R.M. (1998). Dendritic cells induce autoimmune disease and maintain disease via de novo formation of local lymphoid tissue. J. Exp. Med. 188, 1493-1501.
Madaio, M.P. (1999). The role of autoantibodies in the pathogenesis of lupus nephritis. Semin. Nephrol. 19, 48-56.
Mamula, M.J. (1998). Epitope spreading: the role of self peptides and autoantigen processing by B lymphocytes. Immunol. Rev. 164, 231-239.
Mamula, M.J., and Janeway, C.A. Jr. (1993). Do B cells drive the diversification of immune responses? Immunol. Today 14, 151-152.
Mayordomo, J.I., Loftus, D.J., Sakamoto, H., De Ceasre, C.M., Appasamy, P.M., Lotze, M.T., Storkus, W.J., Appella, E., and DeLeo, A.B. (1996). Therapy of murine tumors with p53 wild-type and mutant sequence peptide-based vaccines. J. Exp. Med. 183, 1357-1365.
Mohan, C., Adams, S., Stanik, V., and Datta, S.K. (1993). Nucleosome: a major immunogen for the pathogenic autoantibody-inducing T cells of lupus. J. Exp. Med. 177, 1367-1381.
Mohan, C., Shi, Y., Laman, J.D., and Datta, S.K. (1995). Interaction between CD40 and its ligand gp39 in the development of murine lupus nephritis. J. Immunol. 154, 1470-1480.
Moll, H., Fuchs, H., Blank, C., and Rollinghoff, M. (1993). Langerhans cells transport Leishmania major from the infected skin to the draining lymph node for presentation to antigen-specific T cells. Eur. J. Immunol. 23, 1595-1601.
Morel, L., Tian, X.H., Croker, B.P., and Wakeland, E.K. (1999). Epistatic modifiers of autoimmunity in a murine model of lupus nephritis. Immunity 11, 131-139.
Moudgil, K. D. (1998). Diversification of response to hsp65 during the course of autoimmune arthritis is regulatory rather than pathogenic. Immunol. Rev. 164, 175-184.
Nygard, N.R., McCarthy, D.M., Schiffenbauer, J., and Schwartz, B.D. (1993). Mixed haplotypes and autoimmunity. Immunol. Today 14, 53-56.
Ohashi, P.S., Oehen, S., Buerki, K., Pircher, H., Ohashi, C.T., Odermatt, B., Malissen, B., Zinkernagel, R.M., and Hengartner, H. (1991). Ablation of “tolerance” induction of diabetes by virus infection in viral antigen transgenic mice. Cell 65, 305-317.
Okubo, M., Kokubun, M., Nishimaki, T., Kasukawa, R., Otho, H., Yamamoto, K., and Muller, S. (1992). T cell epitope mapping of U1-A RNP. Arthritis Rheum. 38, 1170-1172.
Okubo, M., Yamamoto, K., Kato, T., Matsuura, N., Nishimaki, T., Kasukawa, R., Ito, K., Mizushima, Y., and Nishioka, K. (1993). Detection and epitope analysis of autoantigen-reactive T cells to the U1-small nuclear ribonucleoprotein A protein in autoimmune disease patients. J. Immunol. 151, 1108-1115.
Perniok, A., Wedekind, F., Herrmann, M., Specker, C., and Schneider, M. (1998). High levels of circulating early apoptotic peripheral blood mononuclear cells in systemic lupus erythematosus. Lupus 7, 113-118.
Pine, J.W. (1997). Dubois’ lupus erythematosus. Editors, Wallace, D.J., and Bevra, H.H.; associated editors, Ouismorio, J.R., Klinenberg 5th ed.
Porgador, A., and Gilboa, E. (1995). Bone marrow-generated dendritic cells pulsed with a class I-restricted peptide are potent inducers of cytotoxic T lymphocytes. J. Exp. Med. 182, 255-260.
Pulendran, B., Smith, J.L., Caspary, G., Brasel, K., Pettit, D., Maraskovsky, E., and Maliszewski, C.R. (1999). Distinct dendritic cell subsets differentially regulate the class of immune response in vivo. Proc. Natl. Acad. Sci. USA 96, 1036-1041.
Reynolds, P., Gordon, T.P., Purcell, A.W., Jackson, D.C., and McCluskey, J. (1996). Hierarchical self-tolerance to T cell determinants within the ubiquitous nuclear self-antigen La (SS-B) permits induction of systemic autoimmunity in normal mice. J. Exp. Med. 184, 1857-1870.
Ronchese, F., and Hausmann, B. (1993). B lymphocytes in vivo fail to prime naïve T cells, but can stimulate antigen-experienced T lymphocytes. J. Exp. Med. 177, 679-690.
Ronchese, F., Hausmann, B., and Le Gros, G. (1994). Interferon-g- and interleukin-4-producing T cells can be primed on dendritic cells in vivo and do not require the presence of B cells. Eur. J. Immunol. 24, 1148-1154.
Rosen, A., and Casciola-Rosen, L. (1999). Autoantigens as substrates for apoptotic proteases: implications for the pathogenesis of systemic autoimmune disease. Cell Death Differ. 6, 6-12.
Roth, R., Gee, R.J., and Mamula, M.J. (1997). B lymphocytes as autoantigen-presenting cells in the amplification of autoimmunity. Ann. N. Y. Acad. Sci. 815, 88-104.
Rovere, P., Manfredi, A.A., Vallinoto, C., Zimmermann, V.S., Fascio, U., Balestrieri, G., Ricciardi-Castagnoli, P., Rugarli, C., Tincani, A., and Sabbadini, M.G. (1998a). Dendritic cells preferentially internalize apoptotic cells opsonized by anti-beta2-glycoprotein I antibodies. J. Autoimmun. 11, 403-411.
Rovere, P., Sabbadini, M.G., Vallinoto, C., Fascio, U., Zimmermann, V.S., Bondanza, A., Ricciardi-Castagnoli, P., and Manfredi, A.A. (1999). Delayed clearance of apoptotic lymphoma cells allows cross-presentation of intracellular antigens by mature dendritic cells. J. Leukoc. Biol. 66, 345-349.
Rovere, P., Vallinoto, C., Bondanza, A., Crosti, M.C., Rescigno, M., Ricciardi-Castagnoli, P., Rugarli, C., and Manfredi, A.A. (1998b). Bystander apoptosis triggers dendritic cell maturation and antigen- presenting function. J. Immunol. 161, 4467-4471.
Rozzo, S.J., Drake, C.G., Chiang, B.L., Gershwin, M.E., and Kotzin B.L. (1994). Evidence for polyclonal T cell activation in murine models of systemic lupus erythematosus. J. Immunol. 153, 1340-1351.
Sallusto, F., and Lanzavecchia, A. (1995). Dendritic cells use macropinocytosis and the mannose receptor to concentrate antigen to the MGC class II compartment. Downregulation by cytokines and bacterial products. J. Exp. Med. 182, 389-400.
Schwartz, R.S., and Stollar, B.D. (1985). Origins of anti-DNA antibodies. J. Clin. Invest. 75, 321-327.
Sercarz, E.E., Lehmann, P.V., Ametani, A., Benichou, G., Miller, A., and Moudgill, K. (1993). Dominance and crypticity of T cell antigenic determinants. Annu. Rev. Immunol. 11, 729-766.
Shi, Y., Kaliyaperumal, A., Lu, L., Southwood, S., Sette, A., Michaels, M.A., and Datta, S.K. (1998). Promiscuous presentation and recognition of nucleosomal autoepitopes in lupus: role of autoimmune T cell receptor alpha chain. J. Exp. Med. 187, 367-378.
Sidman, C.L., Shultz, L.D., Hardy, R.R., Hayakawa, K., and Herzenberg, L.A. (1986). Production of immunoglobulin isotypes by Ly-1+ B cells in viable motheaten and normal mice. Science 232, 1423-1425.
Simpson, E., and Roopenian, D. (1997). Minor histocompatibility antigens. Curr. Opin. Immunol. 9, 655-661.
Singh, R.R., and Hahn, B.H. (1998). Reciprocal T-B determinant spreading develops spontaneously in murine lupus: implications for pathogenesis. Immunol. Rev. 164, 201-208.
Singh, R.R., Ebling, F.M., Sercarz, E.E., and Hahn, B.H. (1995a). Immune tolerance to autoantibody-derived peptides delays development of autoimmunity in murine lupus. J. Clin. Invest. 96, 2990-2996.
Singh, R.R., Kumar, V., Ebling, F.M., Southwood, S., Sette, A., Sercarz, E.E., and Hahn, B.H. (1995b). T cell determinants from autoantibodies to DNA can upregulate autoimmunity in murine systemic lupus erythematosus. J. Exp. Med. 181, 2017-2027.
Sornasse, T., Flamand, V., De Becker, G., Bazin, H., Tielemans, F., Thielemans, K., Urbain, J., Leo, O., and Moser, M. (1992). Antigen-pulsed dendritic cells can efficiently induce an antibody response in vivo. J. Exp. Med. 175, 15-21.
Sullivan, K.E., Petri, M.A., Schmeckpeper, B.J., McLean, R.H., and Winkelstein, J.A. (1994). Prevalence of a mutation causing C2 deficiency in systemic lupus erythematosus. J. Rheumatol. 21, 1128-1133.
Suri, R.M., and Austyn, J.M. (1998). Bacterial lipopolysaccharide contamination of commercial collagen preparations may mediate dendritic cell maturation in culture. J. Immunol. Methods 214, 149-163.
Tan, E.M. (1989). Antinuclear antibodies: diagnostic markers for autoimmune diseases and probes for cell biology. Adv. Immunol. 44, 93-151.
Tan, E.M. (1997). Autoantibodies and autoimmunity: a three-decade perspective. A tribute to Henry G. Kunkel. Ann. N. Y. Acad. Sci. 815, 1-14.
Theofilopoulos, A.N., and Dixon, F.J. (1985). Murine models of systemic lupus erythematosus. Adv. Immunol. 37, 269-379.
Theofilopoulos, A.N., and Lawson, B.R. (1999). Tumor necrosis factor and other cytokines in murine lupus. Ann. Rheum. Dis. 58, 49-55.
Tian, J., Olcott, A.P., Hanssen, L.R., Zekzer, D., Middleton, B., and Kaufman, D.L. (1998). Infectious Th1 and Th2 autoimmunity in diabetes-prone mice. Immunol. Rev. 164, 119-127.
Tisch, R., Yang, X.D., Singer, S.M., Liblau, R.S., Fugger, L., and McDevitt, H.O. (1993). Immune response to glutamic acid decarboxylase correlates with insulitis in non-obese diabetic mice. Nature 366, 72-75.
Topfer, F., Gordon, T., and McCluskey, J. (1995). Intra- and intermolecular spreading of autoimmunity involving the nuclear self-antigens La (SS-B) and Ro (SS-A). Proc. Natl. Acad. Sci. USA 92, 875-879.
Uwatoko, S., Gauthier, V.J., and Mannik, M. (1991). Autoantibodies to the collagen-like region of C1q deposit in glomeruli via C1q in immune deposits. Clin. Immunol. Immunopathol. 61, 268-273.
Vanderlugt, C.L., Begolka, W.S., Neville, K.L., Katz-Levy, Y., Howard, L.M., Eagar, T.N., Bluestone, J.A., and Miller, S.D. (1998). The functional significance of epitope spreading and its regulation by co-stimulatory molecules. Immunol. Rev. 164, 63-72.
Voll, R.E., Herrmann, M., Roth, E.A., Stach, C., Kalden, J.R., and Girkontaite, I. (1997). Immunosuppressive effects of apoptotic cells. Nature 390, 350-351.
Walport, M.J., Davies, K.A., Morley, B.J., and Botto, M. (1997). Complement deficiency and autoimmunity. Ann. N. Y. Acad. Sci. 815, 267-281.
Wang, J., Zheng, L., Lobito, A., Chan, F.K., Dale, J., Sneller, M., Yao, X., Puck, J.M., Straus, S.E. and Lenardo, M.J. (1999). Inherited human caspase 10 mutations underlie defective lymphocyte and dendritic cell apoptosis in autoimmune lymphoproliferative syndrome type II. Cell 98, 47-58.
Wick, G., Hu, Y., Schwarz, S., and Kroemer, G. (1993). Immunoendocrine communication via the hypothalamo-pituitary-adrenal axis in autoimmune disease. Endocr. Rev. 14, 539-563.
Wofsy, D., and Seaman, W.E. (1985). Successful treatment of autoimmunity in NZB/NZW F1 mice with monoclonal antibody to L3T4. J. Exp. Med. 161, 378-391.
Ye, Y.L., and Chiang, B.L. (1998). Reconstitution of severe combined immunodeficient mice with spleen cells from autoimmune NZB × NZW F1 mice. Clin. Exp. Rheumatol. 16, 33-37.
Zieve, G.W., and Sauterer, R.A. Cell biology of the snRNP particles. (1990). Crit. Rev. Biochem. Mol. Biol. 25, 1-46.

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