T-reg mediated suppression of the allograft response in the draining lymph node |
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Authors: | Lee Major K Moore Daniel J Chiaccio Meredith Lian Moh Moh Deng Shaoping Mohiuddin Muhammad Huang Xiaolun Koeberlein Brigitte Zakheim Adam Porrett Paige M Barker Clyde F Caton Andrew J Markmann James F |
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Affiliation: | Department of Surgery, Hospital of the University of Pennsylvania, PA 19104, USA. |
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Abstract: | We previously demonstrated that T-regs inhibit proliferation of graft-reactive T cells in the draining lymph node (DLN), suggesting that this site may be important for regulation. TCR transgenic mice (TS1) specific for viral hemagglutinin (HA) provided antigen-specific T cells for adoptive transfer into syngeneic Balb/c hosts bearing HA+ skin grafts. T-regs were obtained from (TS1xHA28)F1 mice known to have an expanded population of HA-specific T-regs. To determine whether the lymph node is an independent site of suppression, we developed a model in which donor antigen that migrates from the allograft to the DLN drives T-cell activation after graft removal. T-regs that did not encounter the allograft itself remained able to inhibit graft antigen-specific T-cell proliferation in the DLN. Alloantigen-induced regulation can occur in the absence of the graft. This finding identifies the DLN as a potentially critical site of regulation in the early posttransplant period. |
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