Role of IFN-γ in induction of Foxp3 and conversion of CD4+ CD25– T cells to CD4+ Tregs
Zhaojun Wang, Jian Hong, Wei Sun, Guangwu Xu, Ningli Li, Xi Chen, Ailian Liu, Lingyun Xu, Bing Sun, Jingwu Z. Zhang
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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Research Article Immunology

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

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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Figure 6

Suppressing effect of IFN-γ–treated CD4+ CD25– T cells in EAE.

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Suppressing effect of IFN-γ–treated CD4+ ...
CD4+CD25– T cells were purified from GKO mice and cultured in vitro with or without recombinant IFN-γ for 72 hours in the presence of anti-CD3 antibody. The resulting CD4+CD25high T cells from both groups were purified and subsequently transferred to GKO mice (2 × 106 cells per mouse) at day 9 and day 11 after immunization. CD4+CD25+ T cells purified from naive WT mice (Tregs) were transferred at the same cell number (2 × 106 cells per mouse) and under the same experimental conditions without IFN-γ. GKO mice given PBS instead of cells were included as a reference (PBS). Each group consisted of at least 4 mice. Mice were monitored clinically every day for EAE development and progression. The data are presented as EAE clinical scores.