In:
The Journal of Immunology, The American Association of Immunologists, Vol. 184, No. 12 ( 2010-06-15), p. 6629-6636
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-β, 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.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.0904044
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2010
detail.hit.zdb_id:
1475085-5
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