Abstract |
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 naive 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 IAs/ 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.
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Authors | Jayagopala Reddy, Zsolt Illes, Xingmin Zhang, Jeffrey Encinas, Jason Pyrdol, Lindsay Nicholson, Raymond A Sobel, Kai W Wucherpfennig, Vijay K Kuchroo |
Journal | Proceedings of the National Academy of Sciences of the United States of America
(Proc Natl Acad Sci U S A)
Vol. 101
Issue 43
Pg. 15434-9
(Oct 26 2004)
ISSN: 0027-8424 [Print] United States |
PMID | 15492218
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- CD4 Antigens
- Myelin Proteolipid Protein
- Receptors, Interleukin-2
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Topics |
- Amino Acid Sequence
- Animals
- CD4 Antigens
(immunology)
- Encephalomyelitis, Autoimmune, Experimental
(genetics, immunology)
- Genetic Predisposition to Disease
- Mice
- Molecular Sequence Data
- Myelin Proteolipid Protein
(immunology)
- Receptors, Interleukin-2
(immunology)
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