Role of IFN-gamma in Induction of Foxp3 and Conversion of CD4+ CD25- T Cells to CD4+ Tregs

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2006 Aug 15

PMID 16906223

Citations 131

Authors

Zhaojun Wang

Jian Hong

Wei Sun

Guangwu Xu

Ningli Li

Xi Chen

Ailian Liu

Lingyun Xu

Bing Sun

Jingwu Z Zhang

Affiliations

Soon will be listed here.

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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