Promotion of allograft survival by CD4+CD25+ regulatory T cells: evidence for in vivo inhibition of effector cell proliferation.

Lee MK, Moore DJ, Jarrett BP, Lian MM, Deng S, Huang X, Markmann JW, Chiaccio M, Barker CF, Caton AJ, Markmann JF
J Immunol. 2004 172 (11): 6539-44

PMID: 15153467 · DOI:10.4049/jimmunol.172.11.6539

Regulatory T cells preserve tolerance to peripheral self-Ags and may control the response to allogeneic tissues to promote transplantation tolerance. Although prior studies have demonstrated prolonged allograft survival in the presence of regulatory T cells (T-reg), data documenting the capacity of these cells to promote tolerance in immunocompetent transplant models are lacking, and the mechanism of suppression in vivo remains unclear. We used a TCR transgenic model of allograft rejection to characterize the in vivo activity of CD4(+)CD25(+) T-reg. We demonstrate that graft Ag-specific T-reg effectively intercede in the rejection response of naive T cells to established skin allografts. Furthermore, CFSE labeling demonstrates impaired proliferation of naive graft Ag-specific T cells in the draining lymph node in the presence of T-reg. These results confirm the efficacy of T-reg in promoting graft survival and suggest that their suppressive action is accomplished in part through inhibition of proliferation.

MeSH Terms (16)

Animals Antigens, CD Antigens, Differentiation CD4 Antigens CTLA-4 Antigen Graft Rejection Graft Survival Interleukin-10 Lymphocyte Activation Mice Mice, Inbred BALB C Receptors, Interleukin-2 Skin Transplantation T-Lymphocyte Subsets Transforming Growth Factor beta Transplantation, Homologous

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