IFN-γ is critical for disease pathogenesis in a spontaneous mouse model of autoimmune uveitis
作者单位：State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center Sun Yat-sen University
会议名称：《第十届全国免疫学学术大会》
会议日期：2015年
学科分类：1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100212[医学-眼科学] 10[医学]
关 键 词：Autoimmune uveitis IFN-γ mice experimental autoimmune uveitis
摘 要：Purpose: A pathogenic role for IFN-γ producing Th1 cells in autoimmunity was put into question by the recent discovery of IL-17 producing Th17 cells. Like other tissue-specific autoimmunity models induced by autoantigen in complete Freund’s adjuvant(CFA), experimental autoimmune uveitis(EAU) induced by IRBP/CFA is predominantly Th17-dependent and deficiency of IFN-γ exacerbates the disease. To elucidate the role of IFN-γ in IRBP-specific effector T cell responses and pathogenesis of uveitis in a physiologic context without strong exogenous stimuli, we generated an IRBPspecific TCR Tg mouse(R161H) on an IFN-γ knockout(GKO) *** ***: CFA emulsion was injected subcutaneously into R161H-GKO mice at the onset of spontaneous disease. Disease score, T-cell proliferation and T-cell activation, and Taq Man PCR were ***: Essentially all R161 H mice developed severe spontaneous uveitis by 2-3 months of age. The ocular infiltrates contained both IFN-γ and IL-17 producing effector T cells, as well as other inflammatory leukocytes. Deficiency of IFN-γ delayed the onset and markedly decreased the severity of disease. Although the frequency of IRBP-specific T cells and their proliferative responses were not affected, IRBP-activated T cells from R161H-GKO mice transferred attenuated disease to recipient mice, indicating that the defect is T cell-intrinsic. Notably, deficiency of IFN-γ did not precipitate a compensatory Th17 response locally or systemically. However, injection of a blank CFA emulsion into R161H-GKO mice enhanced the IRBP-specific Th17 effector response, increased CCR6+IL-17+ cell infiltration into the eye and restored EAU incidence and ***: Our results point to a pathogenic role of IFN-γ and Th1 cells in spontaneous autoimmune disease. The findings suggest that while forcing a Th17 response can compensate for lack of IFN-γ, the central role of the Th17 effector in tissue-specific autoimmunity, as defined in CFA-driven