Induction of CD4+CD25+ regulatory T cells by copolymer-I through activation of transcription factor Foxp3

被引:213
作者
Hong, J
Li, NL
Zhang, XJ
Zheng, B
Zhang, JWZ
机构
[1] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA
[2] Baylor Coll Med, Dept Immunol, Houston, TX 77030 USA
[3] Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Immunol, Shanghai 200025, Peoples R China
[4] Chinese Acad Sci, Inst Hlth Sci, Joint Immunol Lab, Shanghai 200025, Peoples R China
[5] Shanghai Med Univ 2, Shanghai 200025, Peoples R China
[6] E Inst Shanghai Univ, Shanghai 200025, Peoples R China
关键词
IFN-gamma; multiple sclerosis;
D O I
10.1073/pnas.0502187102
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Copolymerd (COP-1) has unique immune regulatory properties and is a treatment option for multiple sclerosis (MS). This study revealed that CON induced the conversion of peripheral CD4(+)CD25(-) to CD4(+)CD25(+) regulatory T cells through the activation of transcription factor Foxp3. CON treatment led to a significant increase in Foxp3 expression in CD4(+) T cells in MS patients whose Foxp3 expression was reduced at baseline. CD4(+)CD25(+) T cell lines generated by CON expressed high levels of Foxp3 that correlated with an increased regulatory potential. Furthermore, we demonstrated that the induction of Foxp3 in CD4(+) T cells by CON was mediated through its ability to produce IFN-gamma and, to a lesser degree, TGF-beta 1, as shown by antibody blocking and direct cytokine induction of Foxp3 expression in T cells. It was evident that in vitro treatment and administration with CON significantly raised the level of Foxp3 expression in CD4(+) T cells and promoted conversion of CD4(+)CD25(+) regulatory T cells in wild-type 136 mice but not in IFN-gamma knockout mice. This study provides evidence for the role and mechanism of action of CON in the induction of CD4(+)CD25(+) regulatory T cells in general and its relevance to the treatment of MS.
引用
收藏
页码:6449 / 6454
页数:6
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