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Role of IFN-γ in induction of Foxp3 and conversion of CD4+ CD25– T cells to CD4+ Tregs
Zhaojun Wang, … , Bing Sun, Jingwu Z. Zhang
Zhaojun Wang, … , Bing Sun, Jingwu Z. Zhang
Published September 1, 2006
Citation Information: J Clin Invest. 2006;116(9):2434-2441. https://doi.org/10.1172/JCI25826.
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Research Article Immunology

Role of IFN-γ in induction of Foxp3 and conversion of CD4+ CD25– T cells to CD4+ Tregs

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Abstract

IFN-γ is an important Th1 proinflammatory cytokine and has a paradoxical effect on EAE in which disease susceptibility is unexpectedly heightened in IFN-γ–deficient mice. In this study, we provide what we believe is new evidence indicating that IFN-γ 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-γ 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-γ 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-γ, 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-γ in both induction and self regulation of inflammatory processes.

Authors

Zhaojun Wang, Jian Hong, Wei Sun, Guangwu Xu, Ningli Li, Xi Chen, Ailian Liu, Lingyun Xu, Bing Sun, Jingwu Z. Zhang

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