Details

Autor(en) / Beteiligte

• Hong, Jian
• Li, Ningli
• Zhang, Xuejun
• Zheng, Biao
• Zhang, Jingwu Z.
• Chen, Zhu

Titel

Induction of CD4+CD25+Regulatory T Cells by Copolymer-I through Activation of Transcription Factor Foxp3

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2005-05, Vol.102 (18), p.6449-6454

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2005

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• Copolymer-I (COP-I) has unique immune regulatory properties and is a treatment option for multiple sclerosis (MS). This study revealed that COP-I induced the conversion of peripheral CD4+CD25-to CD4+CD25+regulatory T cells through the activation of transcription factor Foxp3. COP-I 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 COP-I 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 COP-I was mediated through its ability to produce IFN-γ and, to a lesser degree, TGF-β1, 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 COP-I significantly raised the level of Foxp3 expression in CD4+T cells and promoted conversion of CD4+CD25+regulatory T cells in wild-type B6 mice but not in IFN-γ knockout mice. This study provides evidence for the role and mechanism of action of COP-I in the induction of CD4+CD25+regulatory T cells in general and its relevance to the treatment of MS.