Long-Term Survival of HLA-DR15⁺ Pig Skin in SCID Mice After Reconstitution With Human Peripheral Blood Mononuclear Cells and Under Short-Term Immunosuppression

In allotransplantation, donor-recipient human leukocyte antigen (HLA) matches improve graft survival. For studies of the role of donor-recipient HLA II matching on xenotransplantation, we successfully generated HLA-DR15⁺ transgenic pigs the the skins of which were transplanted to SCID mice, which were thereafter reconstituted with HLA-DR15⁺ or -DR15^- hPBMC. Cyclosporine was given intraperitoneally to SCID mice for 12 days. Human T cells were observed in SCID mice after reconstitution. Mixed lymphocytes responses showed greater responses by HLA-DR15^- human peripheral blood mononuclear cells (hPBMC) against HLA-DR15⁺ porcine PBMC. HLA-DR15⁺ porcine skins survived more than 100 days in all SCID mice. HLA-DR15⁺ porcine skins were rejected in all non-SCID (Balb/c) mice. The histologic pictures of transplanted HLA-DR15⁺ porcine skins showed surviving porcine epithelium in remodeling murine dermis and little lymphocyte infiltration into the murine dermis. The long-term survival of HLA-DR15⁺ pig skin in all hPBMC-SCID mice might be due to poor engraftment or function of reconstituted T cells. Further studies are needed to clarify the role of donor-recipient matching of HLA-DR15.