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J Immunol. 2010 Jun 15;184(12):6629-36. doi: 10.4049/jimmunol.0904044. Epub 2010 May 7.

TGF-beta-induced myelin peptide-specific regulatory T cells mediate antigen-specific suppression of induction of experimental autoimmune encephalomyelitis.

Author information

1
Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.

Abstract

The low number of natural regulatory T cells (nTregs) in the circulation specific for a particular Ag and concerns about the bystander suppressive capacity of expanded nTregs presents a major clinical challenge for nTreg-based therapeutic treatment of autoimmune diseases. In the current study, we demonstrate that naive CD4+CD25-Foxp3- T cells specific for the myelin proteolipid protein (PLP)139-151 peptide can be converted into CD25+Foxp3+ induced Treg cells (iTregs) when stimulated in the presence of TGF-beta, retinoic acid, and IL-2. These PLP139-151-specific iTregs (139-iTregs) have a phenotype similar to nTregs, but additionally express an intermediate level of CD62L and a high level of CD103. Upon transfer into SJL/J mice, 139-iTregs undergo Ag-driven proliferation and are effective at suppressing induction of experimental autoimmune encephalomyelitis induced by the cognate PLP139-151 peptide, but not PLP178-191 or a mixture of the two peptides. Furthermore, 139-iTregs inhibit delayed-type hypersensitivity responses to PLP139-151, but not PLP178-191, myelin oligodendrocyte glycoprotein (MOG)35-55, or OVA323-339 in mice primed with a mixture of PLP139-151 and the other respective peptides. Additionally, 139-iTregs suppress the proliferation and activation of PLP139-151-, but not MOG35-55-specific CD4+ T cells in SJL/B6 F1 mice primed with a combination of PLP139-151 and MOG35-55. These findings suggest that Ag-specific iTregs are amplified in vivo when exposed to cognate Ag under inflammatory conditions, and these activated iTregs suppress CD4+ responder T cells in an Ag-specific manner.

PMID:
20483764
PMCID:
PMC2882517
DOI:
10.4049/jimmunol.0904044
[Indexed for MEDLINE]
Free PMC Article

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