Role of CD4+ T cells in the rat to mouse cardiac xenotransplantation

T cell subsets involved in rejection of xenografts were analyzed using a rat to mouse cardiac xenotransplant model. Proliferating response and interleulin-2 (IL-2) production in recipients' spleen cells were almost completely abrogated by elimination of L3T4+ T cells, but not by elimination of Lyt2.1+ T cells. Cytotoxic T lymphocyte (CTL) activities were mediated by both L3T4+ and Lyt2.1+ T cells with the help of IL-2-producing L3T4+ T cells. Administration of anti-L3T4 monoclonal antibody (mAb) into recipient mice resulted in a significant prolongation of graft survival (mean graft survival was 29.2 days). Moreover, anti-L3T4 mAb treatment plus thymectomy led to indefinite graft survival. Anti-rat endothelial cell (EC) antibody production in the grafted mice was remarkably suppressed by anti-L3T4 mAb treatment. In contrast, Lyt2.1 mAb treatment did not prolong the graft survival and did not suppress anti-EC antibody production. These results indicated the absolute requirement of L3T4+ T cells in the rejection of rat to mouse cardiac xenografts.