Recovery from experimental allergic encephalomyelitis is TGF-β dependent and associated with increases in CD4+LAP+ and CD4+CD25+ T cells

Xingmin Zhang, Jayagopala Reddy, Hirofumi Ochi, Dan Frenkel, Vijay K. Kuchroo, Howard L. Weiner

Research output: Contribution to journalArticle

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Abstract

SJL mice are highly susceptible to proteolipid protein (PLP) 139-151-induced experimental allergic encephalomyelitis (EAE). The disease is characterized by a relapsing-remitting type of paralysis. However, the mechanism by which animals recover from EAE is poorly understood. Here, we investigated the role of regulatory T cells in the recovery from disease. We found that Forkhead box P3-expressing CD4+CD25+ T cells were increased in the blood, draining lymph node and spleen of EAE-recovered SJL mice. These cells were anergic and inhibited proliferation of CD4+ CD25- T cells to PLP 139-151 or anti-CD3 antibody stimulation. Depletion of CD4-CD25+ T cells during the recovery phase exacerbated disease, resulted in the expansion of IAs/PLP 139-151-tetramer-positive cells and enhanced IFN-γ production. In addition, transforming growth factor-β (TGF-β) was shown to be involved in the recovery from EAE as the percentage of CD4+ cells expressing TGF-β latency-associated peptide (LAP) on the cell surface increased significantly in blood and spleen of EAE-recovered mice as compared with the naive mice and in vivo neutralization of TGF-β abolished recovery from disease. Taken together, our results demonstrate that both CD4+CD25+ and CD4+LAP+ regulatory T cells mediate recovery from PLP 139-151-induced EAE in SJL mice in which TGF-β plays an important role.

Original languageEnglish (US)
Pages (from-to)495-503
Number of pages9
JournalInternational Immunology
Volume18
Issue number4
DOIs
StatePublished - Apr 1 2006

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Autoimmune Experimental Encephalomyelitis
Transforming Growth Factors
T-Lymphocytes
Peptides
Regulatory T-Lymphocytes
Spleen
Peptide T
Paralysis
Anti-Idiotypic Antibodies
Lymph Nodes
myelin proteolipid protein (139-151)

Keywords

  • EAE;LAP;Regulatory T cells;TGF-β

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Recovery from experimental allergic encephalomyelitis is TGF-β dependent and associated with increases in CD4+LAP+ and CD4+CD25+ T cells. / Zhang, Xingmin; Reddy, Jayagopala; Ochi, Hirofumi; Frenkel, Dan; Kuchroo, Vijay K.; Weiner, Howard L.

In: International Immunology, Vol. 18, No. 4, 01.04.2006, p. 495-503.

Research output: Contribution to journalArticle

Zhang, Xingmin ; Reddy, Jayagopala ; Ochi, Hirofumi ; Frenkel, Dan ; Kuchroo, Vijay K. ; Weiner, Howard L. / Recovery from experimental allergic encephalomyelitis is TGF-β dependent and associated with increases in CD4+LAP+ and CD4+CD25+ T cells. In: International Immunology. 2006 ; Vol. 18, No. 4. pp. 495-503.
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