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The Journal of Immunology, 2004, 172: 6539-6544.
Copyright © 2004 by The American Association of Immunologists

Promotion of Allograft Survival by CD4+CD25+ Regulatory T Cells: Evidence for In Vivo Inhibition of Effector Cell Proliferation1

Major K. Lee, IV2,*, Daniel J. Moore2,*, Beth P. Jarrett*, Moh Moh Lian*, Shaoping Deng*, Xiaolun Huang*, Joseph W. Markmann*, Meredith Chiaccio*, Clyde F. Barker*, Andrew J. Caton{dagger} and James F. Markmann3,*

* Harrison Department of Surgical Research, Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA 19104; and {dagger} Wistar Institute, Philadelphia, PA 19104

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.




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