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-me diated rejection of xenografts, In this study, we have evaluated the abilit y of human T cells to mediate rejection of porcine skin grafts in a novel i n vivo experimental system using immunodeficient mice as recipients, Recomb inase-activating gene-1-deficient mice (R-) lacking mature B and T cells we re grafted with porcine skin and received human lymphocytes stimulated in v itro crith irradiated porcine PBMC. Skin grafts on mice given either unsepa rated, activated human lymphocytes . or NK cell-depicted lymphocyte populat ions were rejected within 18 days after adoptive cell transfer, In contrast , skin grafts on mice given T cell-depleted human lymphocytes or saline sho wed no gross or histologic evidence of rejection up to 100 days after adopt ive transfer. Purified CD4(+) T cells were also able to mediate rejection o f porcine skin grafts. These data suggest that human CD4(+) T cells are suf ficient to induce rejection of porcine xenografts. Thus, strategies directe d toward CD4(+) T cells ma effectively prevent cellular rejection of porcin e xenografts in humans.