Activation of recipient T cells recognizing allogeneic MHC molecules displayed on donor leukocytes is known to trigger acute allograft rejection (direct allorecognition). Recently, we have documented the presence of high frequencies of recipient cells displaying donor MHC molecules on their surface (cross-dressed) in the spleen of heart-transplanted mice. We have, now, accumulated strong preliminary evidence suggesting that presentation of donor MHC acquired by recipient APCs plays a key role in the initiation of the T cell pro-inflammatory alloresponse leading to allograft rejection in mice.

In this study, we investigated the presence of donor leukocytes (passenger leukocytes) and recipient cells displaying donor MHC molecules (cross-dressed) in cynomolgus monkeys transplanted with an MHC-mismatched heterotopic heart. After completion of the vascular anastomosis and removal of the vascular clamps, blood was collected at early time points post-transplantation (5-120 minutes). Leukocytes were isolated and analyzed by imaging flow cytometry to detect donor passenger leukocytes and cross-dressed cells. As shown in Table 1, within minutes after graft placement, hundreds of donor leukocytes and thousands of cross-dressed cells were shown to migrate out of the transplant. This is the first demonstration of the presence and trafficking of recipient cells cross-dressed with donor MHC molecules in a primate solid organ transplant model. This finding could serve as a reference for the timing of therapeutic protocols aimed at preventing allorecognition instead of controlling its deleterious effect once it has been initiated.

CITATION INFORMATION: Marino J, Robinson K, Paster J, Hanekamp I, Madsen J, Benichou G. Trafficking of Donor Leukocytes and Recipient Cells Cross-Dressed with Donor MHC Molecules After Transplantation of Cardiac Allografts in Monkeys. Am J Transplant. 2017;17 (suppl 3).

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