Myelin proteolipid protein-specific CD4+CD25+ regulatory cells mediate genetic resistance to experimental autoimmune encephalomyelitis

Jayagopala Reddy, Zsolt Illes, Xingmin Zhang, Jeffrey Encinas, Jason Pyrdol, Lindsay Nicholson, Raymond A. Sobel, Kai W. Wucherpfennig, Vijay K. Kuchroo

Research output: Contribution to journalArticlepeer-review

163 Scopus citations


SJL mice are highly susceptible to experimental autoimmune encephalomyelitis (EAE) induced with myelin proteolipid protein (PLP) peptide 139-151, whereas H-2 congenic B10.S mice are resistant. Immunodominance and susceptibility to EAE are associated with a high precursor frequency of PLP 139-151-specific T cells in the naïve repertoire of SJL mice. To understand the mechanism of EAE resistance in B10.S mice, we determined the precursor frequency of PLP 139-151-reactive T cells in both strains by using IA s/PLP 139-151 tetramers. SJL and B10.S mice had similar frequencies of tetramer-reactive T cells in the naive peripheral repertoire. However, in SJL mice, the majority of PLP 139-151 tetramer-positive cells were in the CD4 +CD25- population, whereas there were more tetramer-positive cells in the CD4+CD25+ population of B10.S mice. Depletion of CD4+CD25+ cells in vivo facilitated the expansion of PLP 139-151-reactive cells with production of T helper 1 cytokines in EAE-resistant B10.S mice. Furthermore, anti-CD25 Ab treatment before immunization resulted in EAE induction in these otherwise resistant mice. These data indicate an important role for autoantigen-specific CD4+CD25+ cells in genetic resistance to autoimmunity.

Original languageEnglish (US)
Pages (from-to)15434-15439
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number43
StatePublished - Oct 26 2004
Externally publishedYes

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Myelin proteolipid protein-specific CD4<sup>+</sup>CD25<sup>+</sup> regulatory cells mediate genetic resistance to experimental autoimmune encephalomyelitis'. Together they form a unique fingerprint.

Cite this