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
Figure 1
Severity of EAE in IFN-γ GKO and WT mice.
Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)