The immunologic mechanisms involved in the destruction of murine cardi
ac allografts were evaluated using MHC-deficient mice. Specifically, w
e examined the survival of immediately vascularized heterotopic adult
cardiac grafts deficient in MHC class I, MHC class II, or both MHC cla
ss I and II antigens following transplantation to allogeneic hosts. We
observed indefinite cardiac graft survival when donors lacked MHC cla
ss II or both MHC I and II antigens. In parallel experiments, we studi
ed the survival of cardiac grafts harvested from normal donors in reci
pients severely depleted of either CD4 (class II-deficient mice) or CD
8 (class I-deficient mice) T cells. Craft survival was dramatically pr
olonged in the absence of CD4 but not CD8 T cells. Collectively, our r
esults demonstrate that the interaction of host CD4 T cells with donor
class II antigens is critical to the rejection of murine cardiac graf
ts.