Influence of Interferon-γ Deficiency in Immune Tolerance Induced by Male Islet Transplantation
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background: Traditionally, interferon-γ (IFN-γ) was regarded as a pro-inflammatory cytokine, however, recent reports suggested role of IFN-γ in immune tolerance. In our previous report, we could induce tolerance to male antigen (HY)just by male islet transplantation in wild type C57BL/6 mice without any immunological intervention. We tried to investigate the influence of IFN-γ deficiency on tolerance induction by male islet transplantation. Methods: To examine the immunogenicity of male tissue in the absence of IFN-γ, we transplanted male IFN-γ knock-out (KO) skin to female IFN-γ KO mice. Next, we analyzed male IFN-γ KO islet to streptozotocin-induced diabetic female IFN-γ KO mice. And, we checked the functionality of grafted islet by graft removal and insulin staining. Results: As our previous results in wild type C57BL/6 mice, female IFN-γ KO mice rejected male IFN-γ KO skin within 29 days, and did not reject male IFN-γ KO islet. The maintenance of normal blood glucose level was dependent on the presence of grafted male islet. And the male islet recipient did not reject 2nd challenge of male islet graft also. Conclusion: Deficiency of IFN-γ does not have influence on the result of male skin graft and male islet transplantation. Conclusively, male islet transplantation induced T cell tolerance is not dependent on the presence of IFN-γ.
Abstract
Background: Traditionally, interferon-γ (IFN-γ) was regarded as a pro-inflammatory cytokine, however, recent reports suggested role of IFN-γ in immune tolerance. In our previous report, we could induce tolerance to male antigen (HY)just by male islet transplantation in wild type C57BL/6 mice without any immunological intervention. We tried to investigate the influence of IFN-γ deficiency on tolerance induction by male islet transplantation. Methods: To examine the immunogenicity of male tissue in the absence of IFN-γ, we transplanted male IFN-γ knock-out (KO) skin to female IFN-γ KO mice. Next, we analyzed male IFN-γ KO islet to streptozotocin-induced diabetic female IFN-γ KO mice. And, we checked the functionality of grafted islet by graft removal and insulin staining. Results: As our previous results in wild type C57BL/6 mice, female IFN-γ KO mice rejected male IFN-γ KO skin within 29 days, and did not reject male IFN-γ KO islet. The maintenance of normal blood glucose level was dependent on the presence of grafted male islet. And the male islet recipient did not reject 2nd challenge of male islet graft also. Conclusion: Deficiency of IFN-γ does not have influence on the result of male skin graft and male islet transplantation. Conclusively, male islet transplantation induced T cell tolerance is not dependent on the presence of IFN-γ.
참고문헌 (29)
- Millrain M, "Examination of HY response: T cell expansion, immunodominance, and cross-priming revealed by HY tetramer analysis", J Immunol, 167, pp.3756~3764 (2001)
- Simpson E, "The male-specific histocompatibility antigen, H-Y: a history of transplantation, immune response genes, sex determination and expression cloning", Annu Rev Immunol, 15, pp.39~61 (1997)
- T-cell regulated tolerance to HY-mismatched skin grafts, "Transplantation", 2008, 1352~1360
- Kelchtermans H, "How interferon-gamma keeps autoimmune diseases in check", Trends Immunol, 29, pp.479~486 (2008)
- Manoury-Schwartz B, "High susceptibility to collagen-induced arthritis in mice lacking IFN-gamma receptors", J Immunol, 158, pp.5501~5506 (1997)
- Vermeire K, "Accelerated collagen-induced arthritis in IFNgamma receptor-deficient mice", J Immunol, 158, pp.5507~5513 (1997)
- Billiau A, "Enhancement of experimental allergic encephalomyelitis in mice by antibodies against IFNgamma", J Immunol, 140, pp.1506~1510 (1988)
- Caspi RR, "Endogenous systemic IFN-gamma has a protective role against ocular autoimmunity in mice", J Immunol, 152, pp.890~899 (1994)
- Eriksson U, "Dual role of the IL-12", IFN-gamma axis in the development of autoimmune myocarditis: induction by IL-12 and protection by IFN-gamma, 2001, pp.167, 5464~5469
- Ferber IA, "Mice with a disrupted IFN-gamma gene are susceptible to the induction of experimental autoimmune encephalomyelitis (EAE)", J Immunol, 156, pp.5~7 (1996)
- Jones LS, "IFN-gamma-deficient mice develop experimental autoimmune uveitis in the context of a deviant effector response", J Immunol, 158, pp.5997~6005 (1997)
- Ring GH, "Increased susceptibility to immunologically mediated glomerulonephritis in IFN-gamma-deficient mice", J Immunol, 163, pp.2243~2248 (1999)
- Willenborg DO, "IFN-gamma plays a critical down-regulatory role in the induction and effector phase of myelin oligodendrocyte glycoprotein-induced autoimmune encephalomyelitis", J Immunol, 157, pp.3223~3227 (1996)
- Nishibori T, "Impaired development of CD4+ CD25+ regulatory T cells in the absence of STAT1: increased susceptibility to autoimmune disease", J Exp Med, 199, pp.25~34 (2004)
- Wang Z, "Role of IFN-gamma in induction of Foxp3 and conversion of CD4+ CD25- T cells to CD4+ Tregs", J Clin Invest, 116, pp.2434~2441 (2006)
- Hong J, "Induction of CD4+CD25+ regulatory T cells by copolymer-I through activation of transcription factor Foxp3", Proc Natl Acad Sci U S A, 102, pp.6449~6454 (2005)
- Feng G, "Exogenous IFN-gamma ex vivo shapes the alloreactive T-cell repertoire by inhibition of Th17 responses and generation of functional Foxp3+ regulatory T cells", Eur J Immunol, 38, pp.2512~2527 (2008)
- Sawitzki B, "IFN-gamma production by alloantigen-reactive regulatory T cells is important for their regulatory function in vivo", J Exp Med, 201, pp.1925~1935 (2005)
- Fallarino F, "Modulation of tryptophan catabolism by regulatory T cells", Nat Immunol, 4, pp.1206~1212 (2003)
- Moffett JR, "Tryptophan and the immune response", Immunol Cell Biol, 81, pp.247~265 (2003)
- Mellor AL, "IDO expression by dendritic cells: tolerance and tryptophan catabolism", Nat Rev Immunol, 4, pp.762~774 (2004)
- Nast CC, "Gamma-interferon gene expression in human renal allograft fine-needle aspirates", Transplantation, 57, pp.498~502 (1994)
- Cobbold SP, "Induction of foxP3+ regulatory T cells in the periphery of T cell receptor transgenic mice tolerized to transplants", J Immunol, 172, pp.6003~6010 (2004)
- Lechler RI, "The complementary roles of deletion and regulation in transplantation tolerance", Nat Rev Immunol, 3, pp.147~158 (2003)
- Li XC, "T cell death and transplantation tolerance", Immunity, 14, pp.407~416 (2001)
- Scully R, "Mechanisms in CD4 antibody-mediated transplantation tolerance: kinetics of induction, antigen dependency and role of regulatory T cells", Eur J Immunol, 24, pp.2383~2392 (1994)
- Waldmann H, "Regulating the immune response to transplants. A role for CD4+ regulatory cells", Immunity, 14, pp.399~406 (2001)
- Zhang L, "Transforming growth factor- beta: an important role in CD4+CD25+ regulatory T cells and immune tolerance", Autoimmunity, 39, pp.269~276 (2006)
- Tanaka K, "PDL1 is required for peripheral transplantation tolerance and protection from chronic allograft rejection", J Immunol, 179, pp.5204~5210 (2007)