SURVIVAL OF MHC-DEFICIENT MOUSE HETEROTOPIC CARDIAC ALLOGRAFTS

The immunologic mechanisms involved in the destruction of murine cardiac allografts were evaluated using MHC-deficient mice. Specifically, we examined the survival of immediately vascularized heterotopic adult cardiac grafts deficient in MHC class I, MHC class II, or both MHC class I and II antigens following transplantation to allogeneic hosts. We observed indefinite cardiac graft survival when donors lacked MHC class II or both MHC I and II antigens. In parallel experiments, we studied the survival of cardiac grafts harvested from normal donors in recipients severely depleted of either CD4 (class II-deficient mice) or CD8 (class I-deficient mice) T cells. Craft survival was dramatically prolonged in the absence of CD4 but not CD8 T cells. Collectively, our results demonstrate that the interaction of host CD4 T cells with donor class II antigens is critical to the rejection of murine cardiac grafts.