*Purpose: Achieving specific long-term allograft survival without ongoing immunosuppression is one of the main objectives in transplantation. Mixed hematopoietic chimerism is a strategy that has achieved tolerance of allogeneic organs in rodents, non-human primates and patients. An essential mechanism behind tolerance in this model is the presentation of donor MHC molecules by APCs in the host’s thymus. In this study, we examined the presence of MHC cross-dressed cells in murine and non-human primate (NHP) mixed chimeras.

*Methods: Conditioned SJL (CD45.1⁺, H2-K^s+) recipient mice received an allogeneic bone marrow (BM) transplant from C57BL6 (CD45.2⁺, H2-K^b+) donors to induce mixed chimerism. Image flow cytometry was used to detect the presence of cross-dressed cells through a period of 100 days after BM transplantation. For cross-dressing studies in NHPs, PBMCs from tolerant chimeric cynomolgus monkeys transplanted with a heart and kidney graft were isolated and stained with anti-MHC class I H38 and BB7.6 anti-MHC class I fluorescent antibodies.

*Results: The thymus and spleen of murine mixed chimeras showed the presence of MHC⁺ donor-derived vesicles cross-dressing mostly recipient CD3⁺ cells, whereas CD45.1⁺ recipient-derived vesicles cross-dressed a combination of CD3+, CD19+ and CD11b/c+ donor cells in the host’s thymus and spleen. At timepoints past 60 days after BM transplantation, the frequency of cross-dressed recipient cells in the thymus was higher than that of donor cells. H38- recipient cells cross-dressed with donor MHC class I (H38+) molecules were detected in the blood of NHPs after induction of chimerism. Work is in progress to evaluate their role in transplant tolerance.

*Conclusions: MHC transfer through cross-dressing occurs in the lymphatic organs of mixed chimeras. This phenomenon might be a critical pathway by which allo-MHC and other donor-derived molecules are presented in the thymus in order to establish allograft tolerance.

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