Role of IFN-gamma in induction of Foxp3 and conversion of CD4+ CD25- T cells to CD4+ Tregs |
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| Authors: | Wang Zhaojun Hong Jian Sun Wei Xu Guangwu Li Ningli Chen Xi Liu Ailian Xu Lingyun Sun Bing Zhang Jingwu Z |
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| Affiliation: | Joint Immunology Laboratory of Institute of Health Sciences, Shanghai JiaoTong University School of Medicine, and Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China. |
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| Abstract: | IFN-gamma is an important Th1 proinflammatory cytokine and has a paradoxical effect on EAE in which disease susceptibility is unexpectedly heightened in IFN-gamma-deficient mice. In this study, we provide what we believe is new evidence indicating that IFN-gamma is critically required for the conversion of CD4+ CD25- T cells to CD4+ Tregs during EAE. In our study, the added severity of EAE in IFN-gamma knockout mice was directly associated with altered encephalitogenic T cell responses, which correlated with reduced frequency and function of CD4+ CD25+ Foxp3+ Tregs when compared with those of WT mice. It was demonstrated in both human and mouse systems that in vitro IFN-gamma treatment of CD4+ CD25- T cells led to conversion of CD4+ Tregs as characterized by increased expression of Foxp3 and enhanced regulatory function. Mouse CD4+ CD25- T cells, when treated in vitro with IFN-gamma, acquired marked regulatory properties as evidenced by suppression of EAE by adoptive transfer. These findings have important implications for the understanding of the complex role of IFN-gamma in both induction and self regulation of inflammatory processes. |
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