Donor exosomes rather than passenger leukocytes initiate alloreactive T cell responses after transplantation

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Science Immunology  14 Jul 2016:
Vol. 1, Issue 1, pp. aaf8759
DOI: 10.1126/sciimmunol.aaf8759

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Transplant ride along

Despite the successful use of organ transplantation in the clinic, the mechanisms behind early rejection of transplants remain unclear. The passenger leukocyte theory suggests that graft leukocytes that express donor major histocompatibility complexes (MHCs) migrate to recipient lymphoid organs, where they activate host T cells. In multiple mouse models of transplantation, Marino et al. found few donor leukocytes in lymph nodes; rather high numbers of recipient antigen-presenting cells (APCs) were present that were cross-dressed with donor MHC. The donor MHC was derived from allogeneic exosomes, which could induce proinflammatory alloimmune responses even without transplantation. These data suggest that cross-dressed recipient APCs rather than passenger leukocytes may contribute to early T cell activation and transplant rejection.