臺灣博碩士論文加值系統

感染性腹膜炎是末期腎病患者進行腹膜透析時最重要的併發症。腹膜炎的發生可能造成透析效能下降，導致腹膜纖維化而造成腹膜透析治療的失敗。腹膜炎是一種局部的發炎反應。當腹膜炎發生時，腹腔中會湧入大量白血球，包括嗜中性球、巨噬細胞及淋巴球等，執行腹膜免疫的功能，對抗外來入侵的病原菌。其中，T淋巴球在腹膜免疫所扮演的功能迄今還不清楚。本研究的目的，是要了解腹膜透析腹膜炎時的腹膜免疫反應，探討腹膜T淋巴球在腹膜免疫反應所扮演的角色，並研究腹膜T淋巴球免疫反應對腹膜炎治療與預後的影響，提供調控腹膜T淋巴球反應之免疫機轉。
本研究分為四部分:第一部分吾人研究腹膜透析腹膜炎時腹膜T淋巴球的反應及表現，包括表面標記蛋白CD4、CD8以及第一型、第二型T細胞分化的測定，並探討腹膜T淋巴球免疫反應與腹膜炎治療反應的關係。第二部分吾人探討不同之腹膜T淋巴球免疫反應，是否影響腹膜長期的透析功能，造成腹膜透析治療預後的不同。第三部分吾人研究第一型及第二型T細胞腹膜免疫反應的調控作用，包括細胞激素及轉錄因子層次的探討，進一步了解T細胞免疫反應影響腹膜透析腹膜炎治療與預後之免疫機轉。第四部分，吾人由細胞層次探討腹膜T淋巴球於腹膜炎的免疫角色，建立體外模式研究T淋巴球與腹膜間皮細胞間的附著及移行作用，於型態學、動態功能及分子生物學觀點，進一步釐清T細胞在腹膜免疫的重要性。
研究結果發現，腹膜第一型/第二型T 細胞免疫反應對腹膜炎的治療反應及預後有決定性的影響。發生腹膜透析腹膜炎時，腹膜T淋巴球主要表現為T helper 1(Th1)-CD4+及T cytotoxic 2(Tc2)-CD8+ T細胞。當腹膜T 淋巴球CD4/CD8比率呈現逐漸增加的趨勢，即Th1-CD4+相對比率上升，可預測其治療反應良好;而CD4/CD8比率呈現逐漸下降的趨勢，即Th1-CD4+相對比率下降，則是治療反應不佳的表徵。長期追蹤其腹膜功能，發現當CD4/CD8的比率呈現逐步減少的趨勢，會伴隨著腹膜腔transforming growth factor-��1(TGF-��1)的持續表現，造成日後腹膜功能變壞及腹膜纖維化的發生。吾人也發現在腹膜炎早期，腹膜透析引流液內表現較高的interleukin(IL)-12與IL-18，誘發腹膜腔內的interferon-�� (IFN-��)產生，作用於後續適應性免疫反應，則表現主要為第一型之T細胞免疫反應，其腹膜T淋巴球第一型T 細胞激素IFN-�蚺帣臚@型T 細胞轉錄因子T box expressed in T-cells(T-bet)之訊息核糖核酸表現均呈現顯著的增加，臨床上則對治療反應迅速，預後良好。吾人進一步建立T細胞與腹膜間皮細胞之離體附著及移行模式，發現無論是主要表現於Th1細胞的integrins ��6��1，或主要表現於Th2細胞的integrins ��4��1，均媒介T細胞與腹膜間皮細胞的附著及移行作用，使T細胞穿過腹膜間皮細胞到達腹膜腔，執行腹膜免疫的功能。
以上之研究結果顯示:(一) 腹膜T 淋巴球CD4/CD8比率之表現型態，可以作為預測腹膜透析腹膜炎之臨床治療反應及長期腹膜功能變化的指標;(二)腹膜透析患者發生腹膜炎時，腹膜免疫反應主要為第一型T細胞免疫反應者，其臨床上的治療反應及預後優於主要為第二型T細胞免疫反應者;(三)細胞層次上， T細胞經由附著分子integrins的媒介，與腹膜間皮細胞產生附著及移行之交互作用，影響腹膜免疫反應。本研究結果證實腹膜T細胞免疫反應在腹膜免疫機制的重要性，建立了腹膜炎免疫療法的理論基礎。應用於臨床上，未來可以調控腹膜炎免疫反應，改善臨床上的治療反應及預後，提供腹膜炎免疫治療的新方向。

Infectious peritonitis is the most serious complication of peritoneal dialysis (PD), and may lead to peritoneal fibrosis and compromise the efficiency of dialysis. Peritonitis is a local inflammatory disorder. Recruitment and infiltration of leukocytes are essential elements of the peritoneal immune response. However, information on the role of T lymphocytes in peritoneal immunity is limited. The purpose of this study is to clarify the role of T lymphocytes in peritoneal defense mechanisms, and their influence on the response to the treatment of peritonitis and on its prognosis in patients undergoing PD.
Four series of experiments were conducted in this study: First, we examined the changes in T-cell subpopulations and cytokine messenger RNA (mRNA) expression patterns during peritonitis in patients treated with PD. These observations were correlated with responses to treatment and with outcomes. Secondly, to determine the influence of peritonitis on peritoneal transport properties and peritoneal fibrosis, we studied the peritoneal dialyzing function and expression pattern of transforming growth factor-��1 (TGF-��1) as a marker of prognosis. Thirdly, To further explore longitudinal changes of peritoneal immunity during PD-related peritonitis and their influence on peritoneal T-cell differentiation, we examined the production of interleukin (IL)-12, IL-18, and interferon-�� (IFN-��) in peritoneal dialysate effluents (PDE) and the kinetics expression of the transcription factors T box expressed in T-cells (T-bet) and guanine adenine thymine adenine binding protein 3 (GATA-3) in peritoneal T cells during peritonitis. Finally, to explore the role of T lymphocytes in peritoneal immunity in cellular level, we examined the interaction between T cells and human peritoneal mesothelial cells (HPMC) by adhesion model and transmigration assay. The expression of integrins were investigated also.
The results showed that the major T-cell phenotypes in PDE during peritonitis were T helper 1 (Th1)-CD4+ and T cytotoxic 2 (Tc2)-CD8+. The serial changes in T-cell subsets in PDE during peritonitis showed two patterns: a progressive increase in the CD4/CD8 ratio in PDE associated with a rapid response to treatment; and a progressive decrease in the CD4/CD8 ratio associated with a delayed response to treatment. A progressive decrease of the CD4/CD8 ratio in PDE correlated with a persistent expression of TGF-��1, and played a pathogenetic role in the evolution of peritonitis, peritoneal equilibration test (PET) deterioration and peritoneal fibrosis. In the early phase of peritonitis, IL-12, IL-18 and IFN-�� levels in PDE were significant greater in the rapid-response group. In the rapid-response group, IFN-�� and T-bet mRNA expression in peritoneal T cells increased, whereas that of GATA-3 decreased over time. Result were opposite in the delayed-response group. In cellular level, we demonstrated that integrins ��6��1 and ��4��1 mediated T cells adherence to and migration across monolayer of HPMC.
This study explores the role of peritoneal T lymphocytes in peritoneal immunity during PD-related peritonitis. These results suggest that patterns of CD4/CD8 T-cell ratio in PDE predict the outcome of peritonitis in patients undergoing PD. These data also suggest local IL-12 and IL-18 production is part of a protective early immune response to PD-related peritonitis. High IL-12 and IL-18 levels in PDE during the early phase of peritonitis correlated with a predominant type 1 immune response and favorable outcome. Furthermore, the results of in vitro study show the potential role of integrins to control and modulate peritoneal T cells immune response. This study enhances our understanding of mechanisms of peritoneal immunity and also offers the target pathway in immunotherapy for PD-related peritonitis.

1. Gokal R, Mallick NP. Peritoneal dialysis. Lancet 1999;353:823-828.
2. Nolph KD, Lindblad AS, Novak JW. Current concepts. Continuous ambulatory peritoneal dialysis. N Engl J Med 1988;318:1595-1600.
3. Pastan S, Bailey J. Dialysis therapy. N Engl J Med 1998;338:1428-1437.
4. Teitelbaum I, Burkart J. Peritoneal dialysis. Am J Kidney Dis 2003;42:1082-1096.
5. Piraino B. Peritonitis as a complication of peritoneal dialysis. J Am Soc Nephrol 1998;9:1956-1964.
6. Davies SJ, Bryan J, Phillips L, Russell GI. Longitudinal changes in peritoneal kinetics: the effects of peritoneal dialysis and peritonitis. Nephrol Dial Transplant 1996;11:498-506.
7. Maiorca R, Vonesh EF, Cavalli P, De Vecchi A, Giangrande A, La Greca G, Scarpioni LL, Bragantini L, Cancarini GC, Cantaluppi A, Castelnovo C, Castiglioni A, Poisetti P, Viglino G. A multicenter, selection-adjusted comparison of patient and technique survivals on CAPD and hemodialysis. Perit Dial Int 1991;11:118-127.
8. Abdel-Rahman EM, Wakeen M, Zimmerman SW. Characteristics of long-term peritoneal dialysis survivors: 18 years experience in one center. Perit Dial Int 1997;17:151-156.
9. Tranaeus A, Heimburger O, Lindholm B. Peritonitis in continuous ambulatory peritoneal dialysis (CAPD): diagnostic findings, therapeutic outcome and complications. Perit Dial Int 1989;9:179-190.
10. Fried LF, Bernardini J, Johnston JR, Piraino B. Peritonitis influences mortality in peritoneal dialysis patients. J Am Soc Nephrol 1996;7:2176-2182.
11. Van Biesen W, Veys N, Vanholder R, Lameire N. Peritoneal-dialysis-related peritonitis: the art of rope-dancing. Nephrol Dial Transplant 2002;17:1878-1882.
12. Holley JL, Bernardini J, Johnston JR, Piraino B. Methicillin-resistant staphylococcal infections in an outpatient peritoneal dialysis program. Am J Kidney Dis 1990;16:142-146.
13. Kavanagh D, Prescott GJ, Mactier RA. Peritoneal dialysis-associated peritonitis in Scotland (1999-2002). Nephrol Dial Transplant 2004;19:2584-2591.
14. Bunke CM, Brier ME, Golper TA. Outcomes of single organism peritonitis in peritoneal dialysis: gram negatives versus gram positives in the Network 9 Peritonitis Study. Kidney Int 1997;52:524-529.
15. Zelenitsky S, Barns L, Findlay I, Alfa M, Ariano R, Fine A, Harding G. Analysis of microbiological trends in peritoneal dialysis-related peritonitis from 1991 to 1998. Am J Kidney Dis 2000;36:1009-1013.
16. Keane WF, Comty CM, Verbrugh HA, Peterson PK. Opsonic deficiency of peritoneal dialysis effluent in continuous ambulatory peritoneal dialysis. Kidney Int 1984;25:539-543.
17. Holmes CJ. Peritoneal host defense mechanisms in peritoneal dialysis. Kidney Int Suppl 1994;48:S58-70.
18. Broche F, Tellado JM. Defense mechanisms of the peritoneal cavity. Curr Opin Crit Care 2001;7:105-116.
19. Topley N. The cytokine network controlling peritoneal inflammation. Perit Dial Int 1995;15:S35-39; discussion S39-40.
20. Medzhitov R, Janeway C, Jr. Innate immunity. N Engl J Med 2000;343:338-344.
21. Topley N, Liberek T, Davenport A, Li FK, Fear H, Williams JD. Activation of inflammation and leukocyte recruitment into the peritoneal cavity. Kidney Int Suppl 1996;56:S17-21.
22. Topley N, Mackenzie R, Jorres A, Coles GA, Davies M, Williams JD. Cytokine networks in continuous ambulatory peritoneal dialysis: interactions of resident cells during inflammation in the peritoneal cavity. Perit Dial Int 1993;13 Suppl 2:S282-285.
23. Rabb H. The T cell as a bridge between innate and adaptive immune systems: implications for the kidney. Kidney Int 2002;61:1935-1946.
24. Dasgupta MK, Larabie M, Halloran PF. Interferon-gamma levels in peritoneal dialysis effluents: relation to peritonitis. Kidney Int 1994;46:475-481.
25. Topley N, Williams JD. Role of the peritoneal membrane in the control of inflammation in the peritoneal cavity. Kidney Int Suppl 1994;48:S71-78.
26. Li FK, Davenport A, Robson RL, Loetscher P, Rothlein R, Williams JD, Topley N. Leukocyte migration across human peritoneal mesothelial cells is dependent on directed chemokine secretion and ICAM-1 expression. Kidney Int 1998;54:2170-2183.
27. Visser CE, Tekstra J, Brouwer-Steenbergen JJ, Tuk CW, Boorsma DM, Sampat-Sardjoepersad SC, Meijer S, Krediet RT, Beelen RH. Chemokines produced by mesothelial cells: huGRO-alpha, IP-10, MCP-1 and RANTES. Clin Exp Immunol 1998;112:270-275.
28. Tekstra J, Visser CE, Tuk CW, Brouwer-Steenbergen JJ, Burger CW, Krediet RT, Beelen RH. Identification of the major chemokines that regulate cell influxes in peritoneal dialysis patients. J Am Soc Nephrol 1996;7:2379-2384.
29. Jose PJ, Collins PD, Perkins JA, Beaubien BC, Totty NF, Waterfield MD, Hsuan J, Williams TJ. Identification of a second neutrophil-chemoattractant cytokine generated during an inflammatory reaction in the rabbit peritoneal cavity in vivo. Purification, partial amino acid sequence and structural relationship to melanoma-growth-stimulatory activity. Biochem J 1991;278 ( Pt 2):493-497.
30. Beaubien BC, Collins PD, Jose PJ, Totty NF, Hsuan J, Waterfield MD, Williams TJ. A novel neutrophil chemoattractant generated during an inflammatory reaction in the rabbit peritoneal cavity in vivo. Purification, partial amino acid sequence and structural relationship to interleukin 8. Biochem J 1990;271:797-801.
31. Betjes MG, Visser CE, Zemel D, Tuk CW, Struijk DG, Krediet RT, Arisz L, Beelen RH. Intraperitoneal interleukin-8 and neutrophil influx in the initial phase of a CAPD peritonitis. Perit Dial Int 1996;16:385-392.
32. Liberek T, Topley N, Luttmann W, Williams JD. Adherence of neutrophils to human peritoneal mesothelial cells: role of intercellular adhesion molecule-1. J Am Soc Nephrol 1996;7:208-217.
33. Jonjic N, Peri G, Bernasconi S, Sciacca FL, Colotta F, Pelicci P, Lanfrancone L, Mantovani A. Expression of adhesion molecules and chemotactic cytokines in cultured human mesothelial cells. J Exp Med 1992;176:1165-1174.
34. Andreoli SP, Mallett C, Williams K, McAteer JA, Rothlein R, Doerschuk CM. Mechanisms of polymorphonuclear leukocyte mediated peritoneal mesothelial cell injury. Kidney Int 1994;46:1100-1109.
35. Cannistra SA, Ottensmeier C, Tidy J, DeFranzo B. Vascular cell adhesion molecule-1 expressed by peritoneal mesothelium partly mediates the binding of activated human T lymphocytes. Exp Hematol 1994;22:996-1002.
36. Zemel D, Koomen GC, Hart AA, ten Berge IJ, Struijk DG, Krediet RT. Relationship of TNF-alpha, interleukin-6, and prostaglandins to peritoneal permeability for macromolecules during longitudinal follow-up of peritonitis in continuous ambulatory peritoneal dialysis. J Lab Clin Med 1993;122:686-696.
37. Zemel D, Imholz AL, de Waart DR, Dinkla C, Struijk DG, Krediet RT. Appearance of tumor necrosis factor-alpha and soluble TNF-receptors I and II in peritoneal effluent of CAPD. Kidney Int 1994;46:1422-1430.
38. Zemel D, Krediet RT, Koomen GC, Kortekaas WM, Geertzen HG, ten Berge RJ. Interleukin-8 during peritonitis in patients treated with CAPD; an in-vivo model of acute inflammation. Nephrol Dial Transplant 1994;9:169-174.
39. Betjes MG, Tuk CW, Visser CE, Zemel D, Krediet RT, Arisz L, Beelen RH. Analysis of the peritoneal cellular immune system during CAPD shortly before a clinical peritonitis. Nephrol Dial Transplant 1994;9:684-692.
40. Lai KN, Lai KB, Lam CW, Chan TM, Li FK, Leung JC. Changes of cytokine profiles during peritonitis in patients on continuous ambulatory peritoneal dialysis. Am J Kidney Dis 2000;35:644-652.
41. Kroemer G, Cuende E, Martinez C. Compartmentalization of the peripheral immune system. Adv Immunol 1993;53:157-216.
42. Ishida I, Verbeek S, Bonneville M, Itohara S, Berns A, Tonegawa S. T-cell receptor gamma delta and gamma transgenic mice suggest a role of a gamma gene silencer in the generation of alpha beta T cells. Proc Natl Acad Sci U S A 1990;87:3067-3071.
43. Hartman J, Maassen V, Rieber P, Fricke H. T lymphocytes from normal human peritoneum are phenotypically different from their counterparts in peripheral blood and CD3- lymphocyte subsets contain mRNA for the recombination activating gene RAG-1. Eur J Immunol 1995;25:2626-2631.
44. Birkhofer A, Rehbock J, Fricke H. T lymphocytes from the normal human peritoneum contain high frequencies of Th2-type CD8+ T cells. Eur J Immunol 1996;26:957-960.
45. Lewis SL, Kutvirt SG, Cooper CL, Bonner PN, Holmes CJ. Characteristics of peripheral and peritoneal lymphocytes from continuous ambulatory peritoneal dialysis patients. Perit Dial Int 1993;13 Suppl 2:S273-277.
46. Fricke H, Hartmann J, Sitter T, Steldinger R, Rieber P, Schiffl H. Continuous ambulatory peritoneal dialysis impairs T lymphocyte selection in the peritoneum. Kidney Int 1996;49:1386-1395.
47. Lewis SL, Bonner PN, Cooper CL, Holmes CJ. Prospective comparison of blood and peritoneal lymphocytes from continuous ambulatory peritoneal dialysis patients. J Clin Lab Immunol 1992;37:3-19.
48. Hausmann MJ, Rogachev B, Weiler M, Chaimovitz C, Douvdevani A. Accessory role of human peritoneal mesothelial cells in antigen presentation and T-cell growth. Kidney Int 2000;57:476-486.
49. Mosmann TR, Coffman RL. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol 1989;7:145-173.
50. Abbas AK, Murphy KM, Sher A. Functional diversity of helper T lymphocytes. Nature 1996;383:787-793.
51. O'Garra A. Cytokines induce the development of functionally heterogeneous T helper cell subsets. Immunity 1998;8:275-283.
52. Seder RA, Paul WE. Acquisition of lymphokine-producing phenotype by CD4+ T cells. Annu Rev Immunol 1994;12:635-673.
53. Rissoan MC, Soumelis V, Kadowaki N, Grouard G, Briere F, de Waal Malefyt R, Liu YJ. Reciprocal control of T helper cell and dendritic cell differentiation. Science 1999;283:1183-1186.
54. Zheng W, Flavell RA. The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells. Cell 1997;89:587-596.
55. Szabo SJ, Kim ST, Costa GL, Zhang X, Fathman CG, Glimcher LH. A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell 2000;100:655-669.
56. Ho IC, Glimcher LH. Transcription: tantalizing times for T cells. Cell 2002;109 Suppl:S109-120.
57. Rengarajan J, Szabo SJ, Glimcher LH. Transcriptional regulation of Th1/Th2 polarization. Immunol Today 2000;21:479-483.
58. Szabo SJ, Sullivan BM, Stemmann C, Satoskar AR, Sleckman BP, Glimcher LH. Distinct effects of T-bet in TH1 lineage commitment and IFN-gamma production in CD4 and CD8 T cells. Science 2002;295:338-342.
59. Pai SY, Truitt ML, Ho IC. GATA-3 deficiency abrogates the development and maintenance of T helper type 2 cells. Proc Natl Acad Sci U S A 2004;101:1993-1998.
60. Holdsworth SR, Kitching AR, Tipping PG. Th1 and Th2 T helper cell subsets affect patterns of injury and outcomes in glomerulonephritis. Kidney Int 1999;55:1198-1216.
61. Inui N, Chida K, Suda T, Nakamura H. TH1/TH2 and TC1/TC2 profiles in peripheral blood and bronchoalveolar lavage fluid cells in pulmonary sarcoidosis. J Allergy Clin Immunol 2001;107:337-344.
62. Butler NS, Monick MM, Yarovinsky TO, Powers LS, Hunninghake GW. Altered IL-4 mRNA stability correlates with Th1 and Th2 bias and susceptibility to hypersensitivity pneumonitis in two inbred strains of mice. J Immunol 2002;169:3700-3709.
63. Romagnani S. Th1 and Th2 in human diseases. Clin Immunol Immunopathol 1996;80:225-235.
64. Romagnani S. The Th1/Th2 paradigm. Immunol Today 1997;18:263-266.
65. Henrich W: Principles and Practice of Dialysis. Baltimore, Maryland, Williams & Wilkins, 1994
66. Peterson PK, Matzke G, Keane WF. Current concepts in the management of peritonitis in patients undergoing continuous ambulatory peritoneal dialysis. Rev Infect Dis 1987;9:604-612.
67. Keane WF, Bailie GR, Boeschoten E, Gokal R, Golper TA, Holmes CJ, Kawaguchi Y, Piraino B, Riella M, Vas S. Adult peritoneal dialysis-related peritonitis treatment recommendations: 2000 update. Perit Dial Int 2000;20:396-411.
68. Khanna R, Nolph KD, Oreopoulos D: The Essentials of Peritoneal Dialysis. Norwell, MA, Kluwer Academic Publishers, 1993
69. Suassuna JH, Das Neves FC, Hartley RB, Ogg CS, Cameron JS. Immunohistochemical studies of the peritoneal membrane and infiltrating cells in normal subjects and in patients on CAPD. Kidney Int 1994;46:443-454.
70. Lin CY, Huang TP. Gene expression and release of interleukin-8 by peritoneal macrophages and polymorphonuclear leukocytes during peritonitis in uremic patients on continuous ambulatory peritoneal dialysis. Nephron 1994;68:437-441.
71. Stylianou E, Jenner LA, Davies M, Coles GA, Williams JD. Isolation, culture and characterization of human peritoneal mesothelial cells. Kidney Int 1990;37:1563-1570.
72. Twardowski ZJ. Clinical value of standardized equilibration tests in CAPD patients. Blood Purif 1989;7:95-108.
73. Kisielow P, von Boehmer H. Development and selection of T cells: facts and puzzles. Adv Immunol 1995;58:87-209.
74. Basson MA, Zamoyska R. The CD4/CD8 lineage decision: integration of signalling pathways. Immunol Today 2000;21:509-514.
75. Evans DM, Zhu G, Duffy DL, Frazer IH, Montgomery GW, Martin NG. A major quantitative trait locus for CD4-CD8 ratio is located on chromosome 11. Genes Immun 2004;5:548-552.
76. Amadori A, Zamarchi R, De Silvestro G, Forza G, Cavatton G, Danieli GA, Clementi M, Chieco-Bianchi L. Genetic control of the CD4/CD8 T-cell ratio in humans. Nat Med 1995;1:1279-1283.
77. Fei GZ, Sylvan SP, Yao GB, Hellstrom UB. Quantitative monitoring of serum hepatitis B virus DNA and blood lymphocyte subsets during combined prednisolone and interferon-alpha therapy in patients with chronic hepatitis B. J Viral Hepat 1999;6:219-227.
78. Moodley YP, Dorasamy T, Venketasamy S, Naicker V, Lalloo UG. Correlation of CD4:CD8 ratio and tumour necrosis factor (TNF)alpha levels in induced sputum with bronchoalveolar lavage fluid in pulmonary sarcoidosis. Thorax 2000;55:696-699.
79. Pedersen C, Dickmeiss E, Gaub J, Ryder LP, Platz P, Lindhardt BO, Lundgren JD. T-cell subset alterations and lymphocyte responsiveness to mitogens and antigen during severe primary infection with HIV: a case series of seven consecutive HIV seroconverters. Aids 1990;4:523-526.
80. Continuous ambulatory peritoneal dialysis (CAPD) peritonitis treatment recommendations: 1989 update. The Ad Hoc Advisory Committee on Peritonitis Management. Perit Dial Int 1989;9:247-256.
81. Seder RA, Boulay JL, Finkelman F, Barbier S, Ben-Sasson SZ, Le Gros G, Paul WE. CD8+ T cells can be primed in vitro to produce IL-4. J Immunol 1992;148:1652-1656.
82. Salgame P, Abrams JS, Clayberger C, Goldstein H, Convit J, Modlin RL, Bloom BR. Differing lymphokine profiles of functional subsets of human CD4 and CD8 T cell clones. Science 1991;254:279-282.
83. Sad S, Marcotte R, Mosmann TR. Cytokine-induced differentiation of precursor mouse CD8+ T cells into cytotoxic CD8+ T cells secreting Th1 or Th2 cytokines. Immunity 1995;2:271-279.
84. Seder RA, Le Gros GG. The functional role of CD8+ T helper type 2 cells. J Exp Med 1995;181:5-7.
85. Romagnani S. Lymphokine production by human T cells in disease states. Annu Rev Immunol 1994;12:227-257.
86. Romagnani S. Biology of human TH1 and TH2 cells. J Clin Immunol 1995;15:121-129.
87. Heaton T, Rowe J, Turner S, Aalberse RC, de Klerk N, Suriyaarachchi D, Serralha M, Holt BJ, Hollams E, Yerkovich S, Holt K, Sly PD, Goldblatt J, Le Souef P, Holt PG. An immunoepidemiological approach to asthma: identification of in-vitro T-cell response patterns associated with different wheezing phenotypes in children. Lancet 2005;365:142-149.
88. Rook GA, Hernandez-Pando R, Dheda K, Teng Seah G. IL-4 in tuberculosis: implications for vaccine design. Trends Immunol 2004;25:483-488.
89. Demissie A, Abebe M, Aseffa A, Rook G, Fletcher H, Zumla A, Weldingh K, Brock I, Andersen P, Doherty TM. Healthy individuals that control a latent infection with Mycobacterium tuberculosis express high levels of Th1 cytokines and the IL-4 antagonist IL-4delta2. J Immunol 2004;172:6938-6943.
90. Choi IS, Koh YI. Effects of BCG revaccination on asthma. Allergy 2003;58:1114-1116.
91. Savignac M, Gomes B, Gallard A, Narbonnet S, Moreau M, Leclerc C, Paulet P, Mariame B, Druet P, Saoudi A, Fournie GJ, Guery JC, Pelletier L. Dihydropyridine receptors are selective markers of Th2 cells and can be targeted to prevent Th2-dependent immunopathological disorders. J Immunol 2004;172:5206-5212.
92. Okubo T, Hagiwara E, Ohno S, Tsuji T, Ihata A, Ueda A, Shirai A, Aoki I, Okuda K, Miyazaki J, Ishigatsubo Y. Administration of an IL-12-encoding DNA plasmid prevents the development of chronic graft-versus-host disease (GVHD). J Immunol 1999;162:4013-4017.
93. Watson CJ, Finlay-Jones JJ, McDonald PJ, Hart PH. IL-4 mRNA expression by peritoneal cells during episodes of peritonitis in patients on continuous ambulatory peritoneal dialysis. Clin Exp Immunol 1995;100:253-261.
94. Lu Y, Hylander B, Brauner A. Interleukin-10, interferon gamma, interleukin-2, and soluble interleukin-2 receptor alpha detected during peritonitis in the dialysate and serum of patients on continuous ambulatory peritoneal dialysis. Perit Dial Int 1996;16:607-612.
95. Shadrin OV, Khar'kovskaia NA, Kaufman O, Tolcheev Iu D, Dronova OM, Malakhova NV, Bykovskaia SN. [The effect of recombinant interleukin-2 on the course of experimental staphylococcal peritonitis in mice]. Biull Eksp Biol Med 1992;114:385-387.
96. Medcalf JF, Harris K, Walls J. Preserving the peritoneum in CAPD. Nephrol Dial Transplant 1997;12:393-395.
97. Leavesley DI, Stanley JM, Faull RJ. Epidermal growth factor modifies the expression and function of extracellular matrix adhesion receptors expressed by peritoneal mesothelial cells from patients on CAPD. Nephrol Dial Transplant 1999;14:1208-1216.
98. Lin CY, Chen WP, Yang LY, Chen A, Huang TP. Persistent transforming growth factor-beta 1 expression may predict peritoneal fibrosis in CAPD patients with frequent peritonitis occurrence. Am J Nephrol 1998;18:513-519.
99. Dobbie JW, Anderson JD, Hind C. Long-term effects of peritoneal dialysis on peritoneal morphology. Perit Dial Int 1994;14 Suppl 3:S16-20.
100. Border WA, Noble NA. Transforming growth factor beta in tissue fibrosis. N Engl J Med 1994;331:1286-1292.
101. Kovacs EJ. Fibrogenic cytokines: the role of immune mediators in the development of scar tissue. Immunol Today 1991;12:17-23.
102. Okamura H, Tsutsi H, Komatsu T, Yutsudo M, Hakura A, Tanimoto T, Torigoe K, Okura T, Nukada Y, Hattori K, et al. Cloning of a new cytokine that induces IFN-gamma production by T cells. Nature 1995;378:88-91.
103. Akira S. The role of IL-18 in innate immunity. Curr Opin Immunol 2000;12:59-63.
104. Dinarello CA. IL-18: A TH1-inducing, proinflammatory cytokine and new member of the IL-1 family. J Allergy Clin Immunol 1999;103:11-24.
105. Puren AJ, Fantuzzi G, Gu Y, Su MS, Dinarello CA. Interleukin-18 (IFNgamma-inducing factor) induces IL-8 and IL-1beta via TNFalpha production from non-CD14+ human blood mononuclear cells. J Clin Invest 1998;101:711-721.
106. Netea MG, Kullberg BJ, Verschueren I, Van Der Meer JW. Interleukin-18 induces production of proinflammatory cytokines in mice: no intermediate role for the cytokines of the tumor necrosis factor family and interleukin-1beta. Eur J Immunol 2000;30:3057-3060.
107. Trinchieri G. Interleukin-12: a proinflammatory cytokine with immunoregulatory functions that bridge innate resistance and antigen-specific adaptive immunity. Annu Rev Immunol 1995;13:251-276.
108. Robinson D, Shibuya K, Mui A, Zonin F, Murphy E, Sana T, Hartley SB, Menon S, Kastelein R, Bazan F, O'Garra A. IGIF does not drive Th1 development but synergizes with IL-12 for interferon-gamma production and activates IRAK and NFkappaB. Immunity 1997;7:571-581.
109. Hsieh CS, Macatonia SE, Tripp CS, Wolf SF, O'Garra A, Murphy KM. Development of TH1 CD4+ T cells through IL-12 produced by Listeria-induced macrophages. Science 1993;260:547-549.
110. Lauw FN, Branger J, Florquin S, Speelman P, van Deventer SJ, Akira S, van der Poll T. IL-18 improves the early antimicrobial host response to pneumococcal pneumonia. J Immunol 2002;168:372-378.
111. Bohn E, Sing A, Zumbihl R, Bielfeldt C, Okamura H, Kurimoto M, Heesemann J, Autenrieth IB. IL-18 (IFN-gamma-inducing factor) regulates early cytokine production in, and promotes resolution of, bacterial infection in mice. J Immunol 1998;160:299-307.
112. Wei XQ, Leung BP, Niedbala W, Piedrafita D, Feng GJ, Sweet M, Dobbie L, Smith AJ, Liew FY. Altered immune responses and susceptibility to Leishmania major and Staphylococcus aureus infection in IL-18-deficient mice. J Immunol 1999;163:2821-2828.
113. Mastroeni P, Clare S, Khan S, Harrison JA, Hormaeche CE, Okamura H, Kurimoto M, Dougan G. Interleukin 18 contributes to host resistance and gamma interferon production in mice infected with virulent Salmonella typhimurium. Infect Immun 1999;67:478-483.
114. Kawakami K, Qureshi MH, Zhang T, Okamura H, Kurimoto M, Saito A. IL-18 protects mice against pulmonary and disseminated infection with Cryptococcus neoformans by inducing IFN-gamma production. J Immunol 1997;159:5528-5534.
115. Sugawara I, Yamada H, Kaneko H, Mizuno S, Takeda K, Akira S. Role of interleukin-18 (IL-18) in mycobacterial infection in IL-18-gene-disrupted mice. Infect Immun 1999;67:2585-2589.
116. Weijer S, Sewnath ME, de Vos AF, Florquin S, van der Sluis K, Gouma DJ, Takeda K, Akira S, van der Poll T. Interleukin-18 facilitates the early antimicrobial host response to Escherichia coli peritonitis. Infect Immun 2003;71:5488-5497.
117. Dybing JK, Walters N, Pascual DW. Role of endogenous interleukin-18 in resolving wild-type and attenuated Salmonella typhimurium infections. Infect Immun 1999;67:6242-6248.
118. Neighbors M, Xu X, Barrat FJ, Ruuls SR, Churakova T, Debets R, Bazan JF, Kastelein RA, Abrams JS, O'Garra A. A critical role for interleukin 18 in primary and memory effector responses to Listeria monocytogenes that extends beyond its effects on Interferon gamma production. J Exp Med 2001;194:343-354.
119. Vankayalapati R, Wizel B, Weis SE, Samten B, Girard WM, Barnes PF. Production of interleukin-18 in human tuberculosis. J Infect Dis 2000;182:234-239.
120. Garcia VE, Uyemura K, Sieling PA, Ochoa MT, Morita CT, Okamura H, Kurimoto M, Rea TH, Modlin RL. IL-18 promotes type 1 cytokine production from NK cells and T cells in human intracellular infection. J Immunol 1999;162:6114-6121.
121. Wagner RD, Steinberg H, Brown JF, Czuprynski CJ. Recombinant interleukin-12 enhances resistance of mice to Listeria monocytogenes infection. Microb Pathog 1994;17:175-186.
122. Flynn JL, Goldstein MM, Triebold KJ, Sypek J, Wolf S, Bloom BR. IL-12 increases resistance of BALB/c mice to Mycobacterium tuberculosis infection. J Immunol 1995;155:2515-2524.
123. Greenberger MJ, Kunkel SL, Strieter RM, Lukacs NW, Bramson J, Gauldie J, Graham FL, Hitt M, Danforth JM, Standiford TJ. IL-12 gene therapy protects mice in lethal Klebsiella pneumonia. J Immunol 1996;157:3006-3012.
124. Metzger DW, Raeder R, Van Cleave VH, Boyle MD. Protection of mice from group A streptococcal skin infection by interleukin-12. J Infect Dis 1995;171:1643-1645.
125. Kincy-Cain T, Clements JD, Bost KL. Endogenous and exogenous interleukin-12 augment the protective immune response in mice orally challenged with Salmonella dublin. Infect Immun 1996;64:1437-1440.
126. Brunda MJ. Interleukin-12. J Leukoc Biol 1994;55:280-288.
127. Ahn HJ, Maruo S, Tomura M, Mu J, Hamaoka T, Nakanishi K, Clark S, Kurimoto M, Okamura H, Fujiwara H. A mechanism underlying synergy between IL-12 and IFN-gamma-inducing factor in enhanced production of IFN-gamma. J Immunol 1997;159:2125-2131.
128. Kohno K, Kataoka J, Ohtsuki T, Suemoto Y, Okamoto I, Usui M, Ikeda M, Kurimoto M. IFN-gamma-inducing factor (IGIF) is a costimulatory factor on the activation of Th1 but not Th2 cells and exerts its effect independently of IL-12. J Immunol 1997;158:1541-1550.
129. Micallef MJ, Ohtsuki T, Kohno K, Tanabe F, Ushio S, Namba M, Tanimoto T, Torigoe K, Fujii M, Ikeda M, Fukuda S, Kurimoto M. Interferon-gamma-inducing factor enhances T helper 1 cytokine production by stimulated human T cells: synergism with interleukin-12 for interferon-gamma production. Eur J Immunol 1996;26:1647-1651.
130. Steinhauser ML, Hogaboam CM, Lukacs NW, Strieter RM, Kunkel SL. Multiple roles for IL-12 in a model of acute septic peritonitis. J Immunol 1999;162:5437-5443.
131. Matsukawa A, Kaplan MH, Hogaboam CM, Lukacs NW, Kunkel SL. Pivotal role of signal transducer and activator of transcription (Stat)4 and Stat6 in the innate immune response during sepsis. J Exp Med 2001;193:679-688.
132. Nakahira M, Tomura M, Iwasaki M, Ahn HJ, Bian Y, Hamaoka T, Ohta T, Kurimoto M, Fujiwara H. An absolute requirement for STAT4 and a role for IFN-gamma as an amplifying factor in IL-12 induction of the functional IL-18 receptor complex. J Immunol 2001;167:1306-1312.
133. Lamperi S, Carozzi S. Suppressor resident peritoneal macrophages and peritonitis incidence in continuous ambulatory peritoneal dialysis. Nephron 1986;44:219-225.
134. Lamperi S, Carozzi S. Interferon-gamma (IFN-gamma) as in vitro enhancing factor of peritoneal macrophage defective bactericidal activity during continuous ambulatory peritoneal dialysis (CAPD). Am J Kidney Dis 1988;11:225-230.
135. Hatton RD, Weaver CT. Immunology. T-bet or not T-bet. Science 2003;302:993-994.
136. Robinson DS, O'Garra A. Further checkpoints in Th1 development. Immunity 2002;16:755-758.
137. Farrar JD, Asnagli H, Murphy KM. T helper subset development: roles of instruction, selection, and transcription. J Clin Invest 2002;109:431-435.
138. Mullen AC, High FA, Hutchins AS, Lee HW, Villarino AV, Livingston DM, Kung AL, Cereb N, Yao TP, Yang SY, Reiner SL. Role of T-bet in commitment of TH1 cells before IL-12-dependent selection. Science 2001;292:1907-1910.
139. Lighvani AA, Frucht DM, Jankovic D, Yamane H, Aliberti J, Hissong BD, Nguyen BV, Gadina M, Sher A, Paul WE, O'Shea JJ. T-bet is rapidly induced by interferon-gamma in lymphoid and myeloid cells. Proc Natl Acad Sci U S A 2001;98:15137-15142.
140. Afkarian M, Sedy JR, Yang J, Jacobson NG, Cereb N, Yang SY, Murphy TL, Murphy KM. T-bet is a STAT1-induced regulator of IL-12R expression in naive CD4+ T cells. Nat Immunol 2002;3:549-557.
141. Zhang DH, Cohn L, Ray P, Bottomly K, Ray A. Transcription factor GATA-3 is differentially expressed in murine Th1 and Th2 cells and controls Th2-specific expression of the interleukin-5 gene. J Biol Chem 1997;272:21597-21603.
142. Ouyang W, Ranganath SH, Weindel K, Bhattacharya D, Murphy TL, Sha WC, Murphy KM. Inhibition of Th1 development mediated by GATA-3 through an IL-4-independent mechanism. Immunity 1998;9:745-755.
143. Ouyang W, Lohning M, Gao Z, Assenmacher M, Ranganath S, Radbruch A, Murphy KM. Stat6-independent GATA-3 autoactivation directs IL-4-independent Th2 development and commitment. Immunity 2000;12:27-37.
144. Takemoto N, Kamogawa Y, Jun Lee H, Kurata H, Arai KI, O'Garra A, Arai N, Miyatake S. Cutting edge: chromatin remodeling at the IL-4/IL-13 intergenic regulatory region for Th2-specific cytokine gene cluster. J Immunol 2000;165:6687-6691.
145. Lee HJ, Takemoto N, Kurata H, Kamogawa Y, Miyatake S, O'Garra A, Arai N. GATA-3 induces T helper cell type 2 (Th2) cytokine expression and chromatin remodeling in committed Th1 cells. J Exp Med 2000;192:105-115.
146. Agarwal S, Avni O, Rao A. Cell-type-restricted binding of the transcription factor NFAT to a distal IL-4 enhancer in vivo. Immunity 2000;12:643-652.
147. Lee GR, Fields PE, Flavell RA. Regulation of IL-4 gene expression by distal regulatory elements and GATA-3 at the chromatin level. Immunity 2001;14:447-459.
148. Loots GG, Locksley RM, Blankespoor CM, Wang ZE, Miller W, Rubin EM, Frazer KA. Identification of a coordinate regulator of interleukins 4, 13, and 5 by cross-species sequence comparisons. Science 2000;288:136-140.
149. Mohrs M, Blankespoor CM, Wang ZE, Loots GG, Afzal V, Hadeiba H, Shinkai K, Rubin EM, Locksley RM. Deletion of a coordinate regulator of type 2 cytokine expression in mice. Nat Immunol 2001;2:842-847.
150. Ansel KM, Lee DU, Rao A. An epigenetic view of helper T cell differentiation. Nat Immunol 2003;4:616-623.
151. Siegel MD, Zhang DH, Ray P, Ray A. Activation of the interleukin-5 promoter by cAMP in murine EL-4 cells requires the GATA-3 and CLE0 elements. J Biol Chem 1995;270:24548-24555.
152. Kishikawa H, Sun J, Choi A, Miaw SC, Ho IC. The cell type-specific expression of the murine IL-13 gene is regulated by GATA-3. J Immunol 2001;167:4414-4420.
153. Zhang DH, Yang L, Ray A. Differential responsiveness of the IL-5 and IL-4 genes to transcription factor GATA-3. J Immunol 1998;161:3817-3821.
154. Zhang DH, Yang L, Cohn L, Parkyn L, Homer R, Ray P, Ray A. Inhibition of allergic inflammation in a murine model of asthma by expression of a dominant-negative mutant of GATA-3. Immunity 1999;11:473-482.
155. Betjes MG, Tuk CW, Struijk DG, Krediet RT, Arisz L, Hoefsmit EC, Beelen RH. Immuno-effector characteristics of peritoneal cells during CAPD treatment: a longitudinal study. Kidney Int 1993;43:641-648.
156. Berguer R, Ferrick DA. Differential production of intracellular gamma interferon in alpha beta and gamma delta T-cell subpopulations in response to peritonitis. Infect Immun 1995;63:4957-4958.
157. Goldman M, Vandenabeele P, Moulart J, Amraoui Z, Abramowicz D, Nortier J, Vanherweghem JL, Fiers W. Intraperitoneal secretion of interleukin-6 during continuous ambulatory peritoneal dialysis. Nephron 1990;56:277-280.
158. Topley N, Jorres A, Luttmann W, Petersen MM, Lang MJ, Thierauch KH, Muller C, Coles GA, Davies M, Williams JD. Human peritoneal mesothelial cells synthesize interleukin-6: induction by IL-1 beta and TNF alpha. Kidney Int 1993;43:226-233.
159. Topley N, Brown Z, Jorres A, Westwick J, Davies M, Coles GA, Williams JD. Human peritoneal mesothelial cells synthesize interleukin-8. Synergistic induction by interleukin-1 beta and tumor necrosis factor-alpha. Am J Pathol 1993;142:1876-1886.
160. Visser CE, Steenbergen JJ, Betjes MG, Meijer S, Arisz L, Hoefsmit EC, Krediet RT, Beelen RH. Interleukin-8 production by human mesothelial cells after direct stimulation with staphylococci. Infect Immun 1995;63:4206-4209.
161. Betjes MG, Tuk CW, Struijk DG, Krediet RT, Arisz L, Hart M, Beelen RH. Interleukin-8 production by human peritoneal mesothelial cells in response to tumor necrosis factor-alpha, interleukin-1, and medium conditioned by macrophages cocultured with Staphylococcus epidermidis. J Infect Dis 1993;168:1202-1210.
162. Witowski J, Pawlaczyk K, Breborowicz A, Scheuren A, Kuzlan-Pawlaczyk M, Wisniewska J, Polubinska A, Friess H, Gahl GM, Frei U, Jorres A. IL-17 stimulates intraperitoneal neutrophil infiltration through the release of GRO alpha chemokine from mesothelial cells. J Immunol 2000;165:5814-5821.
163. Douvdevani A, Rapoport J, Konforty A, Argov S, Ovnat A, Chaimovitz C. Human peritoneal mesothelial cells synthesize IL-1 alpha and beta. Kidney Int 1994;46:993-1001.
164. Lanfrancone L, Boraschi D, Ghiara P, Falini B, Grignani F, Peri G, Mantovani A, Pelicci PG. Human peritoneal mesothelial cells produce many cytokines (granulocyte colony-stimulating factor [CSF], granulocyte-monocyte-CSF, macrophage-CSF, interleukin-1 [IL-1], and IL-6) and are activated and stimulated to grow by IL-1. Blood 1992;80:2835-2842.
165. Goodman RB, Wood RG, Martin TR, Hanson-Painton O, Kinasewitz GT. Cytokine-stimulated human mesothelial cells produce chemotactic activity for neutrophils including NAP-1/IL-8. J Immunol 1992;148:457-465.
166. Topley N, Mackenzie RK, Williams JD. Macrophages and mesothelial cells in bacterial peritonitis. Immunobiology 1996;195:563-573.
167. Topley N, Petersen MM, Mackenzie R, Neubauer A, Stylianou E, Kaever V, Davies M, Coles GA, Jorres A, Williams JD. Human peritoneal mesothelial cell prostaglandin synthesis: induction of cyclooxygenase mRNA by peritoneal macrophage-derived cytokines. Kidney Int 1994;46:900-909.
168. Coene MC, Van Hove C, Claeys M, Herman AG. Arachidonic acid metabolism by cultured mesothelial cells. Different transformations of exogenously added and endogenously. Biochim Biophys Acta 1982;710:437-445.
169. Coene MC, Solheid C, Claeys M, Herman AG. Prostaglandin production by cultured mesothelial cells. Arch Int Pharmacodyn Ther 1981;249:316-318.
170. Bult H, Coene MC, Rampart M, Herman AG. Complement derived factors and prostacyclin formation by rabbit isolated peritoneum and cultured mesothelial cells. Agents Actions Suppl 1984;14:237-247.
171. Bittinger F, Klein CL, Skarke C, Brochhausen C, Walgenbach S, Rohrig O, Kohler H, Kirkpatrick CJ. PECAM-1 expression in human mesothelial cells: an in vitro study. Pathobiology 1996;64:320-327.
172. Basok A, Shnaider A, Man L, Chaimovitz C, Douvdevani A. CD40 is expressed on human peritoneal mesothelial cells and upregulates the production of interleukin-15 and RANTES. J Am Soc Nephrol 2001;12:695-702.
173. Hynes RO. Integrins: versatility, modulation, and signaling in cell adhesion. Cell 1992;69:11-25.
174. Albelda SM, Buck CA. Integrins and other cell adhesion molecules. Faseb J 1990;4:2868-2880.
175. Clark EA, Brugge JS. Integrins and signal transduction pathways: the road taken. Science 1995;268:233-239.
176. Sims TN, Dustin ML. The immunological synapse: integrins take the stage. Immunol Rev 2002;186:100-117.
177. von Andrian UH, Mackay CR. T-cell function and migration. Two sides of the same coin. N Engl J Med 2000;343:1020-1034.
178. Westermann J, Engelhardt B, Hoffmann JC. Migration of T cells in vivo: molecular mechanisms and clinical implications. Ann Intern Med 2001;135:279-295.
179. D'Ambrosio D, Iellem A, Colantonio L, Clissi B, Pardi R, Sinigaglia F. Localization of Th-cell subsets in inflammation: differential thresholds for extravasation of Th1 and Th2 cells. Immunol Today 2000;21:183-186.
180. Hogg N, Laschinger M, Giles K, McDowall A. T-cell integrins: more than just sticking points. J Cell Sci 2003;116:4695-4705.
181. Colantonio L, Iellem A, Clissi B, Pardi R, Rogge L, Sinigaglia F, D'Ambrosio D. Upregulation of integrin alpha6/beta1 and chemokine receptor CCR1 by interleukin-12 promotes the migration of human type 1 helper T cells. Blood 1999;94:2981-2989.
182. Clissi B, D'Ambrosio D, Geginat J, Colantonio L, Morrot A, Freshney NW, Downward J, Sinigaglia F, Pardi R. Chemokines fail to up-regulate beta 1 integrin-dependent adhesion in human Th2 T lymphocytes. J Immunol 2000;164:3292-3300.
183. Lim YC, Wakelin MW, Henault L, Goetz DJ, Yednock T, Cabanas C, Sanchez-Madrid F, Lichtman AH, Luscinskas FW. Alpha4beta1-integrin activation is necessary for high-efficiency T-cell subset interactions with VCAM-1 under flow. Microcirculation 2000;7:201-214.
184. Constant SL, Bottomly K. Induction of Th1 and Th2 CD4+ T cell responses: the alternative approaches. Annu Rev Immunol 1997;15:297-322.
185. Springer TA. Adhesion receptors of the immune system. Nature 1990;346:425-434.
186. Zeillemaker AM, Mul FP, Hoynck van Papendrecht AA, Leguit P, Verbrugh HA, Roos D. Neutrophil adherence to and migration across monolayers of human peritoneal mesothelial cells. The role of mesothelium in the influx of neutrophils during peritonitis. J Lab Clin Med 1996;127:279-286.
187. Robson RL, McLoughlin RM, Witowski J, Loetscher P, Wilkinson TS, Jones SA, Topley N. Differential regulation of chemokine production in human peritoneal mesothelial cells: IFN-gamma controls neutrophil migration across the mesothelium in vitro and in vivo. J Immunol 2001;167:1028-1038.