We have studied the trafficking of donor passenger leukocytes and donor MHC presentation in the lymphoid organs of mice having received an MHC-mismatched skin or heart transplant. After skin grafting, we observed a lack of migrating donor passenger leukocytes. On the contrary, high numbers of recipient dendritic cells and some B cells displaying donor MHC antigens on their surface. The majority of transferred allogeneic MHC molecules were MHC class II proteins carried by donor-derived vesicles secreted mainly but not exclusively by donor dendritic cells and B cells. Alternatively, in heart-transplanted mice, we found low but significant numbers of donor leukocytes (100/million cells) spread in draining, non-draining lymph nodes and the spleen. However, the frequency of these cells declined markedly from day 1 through 7 post-transplantation. Alternatively, we detected high numbers of recipient cells cross-dressed with donor MHC (>2000/million cells) in the spleen of recipients. This number gradually increased to reach over 15,000 cross-dressed cells/million spleen cells at day 10 post-transplantation. The vast majority (> 80%) of host cross-dressed cells and donor passenger leukocytes found in the spleen of heart-transplanted mice were CD20⁺ B cells, while no CD11c⁺ DCs were observed. Finally, we showed that recipient cells cross-dressed with donor MHC molecules could activate direct alloresponses in vitro and in vivo. Altogether, our study support the view that the presentation of donor MHC by host APCs in recipient lymphoid organs is the main mechanism underlying sensitization of alloreactive T cells after transplantation.

CITATION INFORMATION: Marino J, Paster J, Crosby P, Uehara M, Mordecai S, Abdi R, Tocco G, Benichou G. Direct Alloimmunity Is Driven by Recipient APCs Displaying Donor MHC Molecules. Am J Transplant. 2016;16 (suppl 3).

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