Human CD4+ T cells mediate rejection of porcine xenografts

It has previously been demonstrated that xenograft rejection in rodents is dependent on CD4(+) T cells. However, because of the lack of an appropriate in vivo model, Little is known about the cellular basis of human T cell-mediated rejection of xenografts, In this study, we have evaluated the ability of human T cells to mediate rejection of porcine skin grafts in a novel in vivo experimental system using immunodeficient mice as recipients, Recombinase-activating gene-1-deficient mice (R-) lacking mature B and T cells were grafted with porcine skin and received human lymphocytes stimulated in vitro crith irradiated porcine PBMC. Skin grafts on mice given either unseparated, activated human lymphocytes . or NK cell-depicted lymphocyte populations were rejected within 18 days after adoptive cell transfer, In contrast, skin grafts on mice given T cell-depleted human lymphocytes or saline showed no gross or histologic evidence of rejection up to 100 days after adoptive transfer. Purified CD4(+) T cells were also able to mediate rejection of porcine skin grafts. These data suggest that human CD4(+) T cells are sufficient to induce rejection of porcine xenografts. Thus, strategies directed toward CD4(+) T cells ma effectively prevent cellular rejection of porcine xenografts in humans.