In:
The Journal of Immunology, The American Association of Immunologists, Vol. 181, No. 11 ( 2008-12-01), p. 7499-7506
Abstract:
We have previously shown that HLA-DQA1, a peptide derived from a highly conserved region of MHC class II, prevents alloreactive T cell priming and effector function in vivo, although underlying mechanisms are obscure. In this study, we demonstrate that 28% of mice treated with HLA-DQA1 combined with low-dose rapamycin achieved permanent engraftment of fully MHC-disparate islet allografts and significantly prolonged survival in the remaining animals (log rank, p & lt; 0.001). Immunohistologic examination of the grafts from HLA-DQA1/rapamycin-treated animals revealed up-regulated expression of TGF-ß and FoxP3. In vivo administration of blocking anti-TGF-ß or depleting anti-CD25 mAb augmented T cell alloimmunity and prevented the long-term engraft induced by HLA-DQA1. In vitro experiments further showed that HLA-DQA1 induced differentiation of CD4+ T cells into CD4+CD25+FoxP3+ regulatory T cells. Together, these data provide the first demonstration that HLA-DQA1, a MHC class II-derived peptide, can prolong allograft survival via a TGF-β and regulatory T cell-dependent mechanisms.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.181.11.7499
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2008
detail.hit.zdb_id:
1475085-5
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