Multiple Sclerosis Research Today is a free monthly online journal that collates and summarizes the latest research about Multiple Sclerosis, including details on diagnosis, symptoms, treatment, prognosis.

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

Hong J, Li N, Zhang X, Zheng B, Zhang JZ

Joint Immunology Laboratory of Institute of Health Sciences and Shanghai Institute of Immunology, Chinese Academy of Sciences and Shanghai Second Medical University, Shanghai 200025, China.

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-gamma and, to a lesser degree, TGF-beta1, 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-gamma 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.

Published 4 May 2005 in Proc Natl Acad Sci U S A, 102(18): 6449-54.
Full-text of this article is available online (may require subscription).

© 2004-2008 Multiple Sclerosis Research Today. All Rights Reserved.