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 journalArticle

160 Citations (Scopus)

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 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
Volume101
Issue number43
DOIs
StatePublished - Oct 26 2004

Fingerprint

Myelin Proteolipid Protein
Autoimmune Experimental Encephalomyelitis
T-Lymphocytes
Autoantigens
Autoimmunity
Population
myelin proteolipid protein (139-151)
Immunization

ASJC Scopus subject areas

  • General

Cite this

Myelin proteolipid protein-specific CD4+CD25+ regulatory cells mediate genetic resistance to experimental autoimmune encephalomyelitis. / Reddy, Jayagopala; Illes, Zsolt; Zhang, Xingmin; Encinas, Jeffrey; Pyrdol, Jason; Nicholson, Lindsay; Sobel, Raymond A.; Wucherpfennig, Kai W.; Kuchroo, Vijay K.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 101, No. 43, 26.10.2004, p. 15434-15439.

Research output: Contribution to journalArticle

Reddy, Jayagopala ; Illes, Zsolt ; Zhang, Xingmin ; Encinas, Jeffrey ; Pyrdol, Jason ; Nicholson, Lindsay ; Sobel, Raymond A. ; Wucherpfennig, Kai W. ; Kuchroo, Vijay K. / Myelin proteolipid protein-specific CD4+CD25+ regulatory cells mediate genetic resistance to experimental autoimmune encephalomyelitis. In: Proceedings of the National Academy of Sciences of the United States of America. 2004 ; Vol. 101, No. 43. pp. 15434-15439.
@article{8ceef324372a4c989a2c1f0d76e36a48,
title = "Myelin proteolipid protein-specific CD4+CD25+ regulatory cells mediate genetic resistance to experimental autoimmune encephalomyelitis",
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 na{\"i}ve 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.",
author = "Jayagopala Reddy and Zsolt Illes and Xingmin Zhang and Jeffrey Encinas and Jason Pyrdol and Lindsay Nicholson and Sobel, {Raymond A.} and Wucherpfennig, {Kai W.} and Kuchroo, {Vijay K.}",
year = "2004",
month = "10",
day = "26",
doi = "10.1073/pnas.0404444101",
language = "English (US)",
volume = "101",
pages = "15434--15439",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "43",

}

TY - JOUR

T1 - Myelin proteolipid protein-specific CD4+CD25+ regulatory cells mediate genetic resistance to experimental autoimmune encephalomyelitis

AU - Reddy, Jayagopala

AU - Illes, Zsolt

AU - Zhang, Xingmin

AU - Encinas, Jeffrey

AU - Pyrdol, Jason

AU - Nicholson, Lindsay

AU - Sobel, Raymond A.

AU - Wucherpfennig, Kai W.

AU - Kuchroo, Vijay K.

PY - 2004/10/26

Y1 - 2004/10/26

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=7444250675&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=7444250675&partnerID=8YFLogxK

U2 - 10.1073/pnas.0404444101

DO - 10.1073/pnas.0404444101

M3 - Article

C2 - 15492218

AN - SCOPUS:7444250675

VL - 101

SP - 15434

EP - 15439

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 43

ER -