Acute rejection of vascular heart allografts by perforin‐deficient mice

Abstract

To study the role of perforin in cell‐mediated graft rejection, vascularized hearts were grafted to perforin‐deficient C57BL/6 and control C57BL/6 recipient mice. Fully allogeneic heart grafts (BALB/c) were acutely rejected by both recipients within 6 days. Peritoneal exudate lymphocytes from control mice but not from perforin‐deficient mice exhibit a strong alloreactive cytotoxic activity in vitro. Histological analysis of the rejected tissues demonstrated extensive mononuclear cell infiltrates in both recipients. Flow cytometry analysis and immunohistology of graft‐infiltrating cells showed similar proportions of lymphocyte subsets (CD8 ≧ CD4). Collectively, these data indicate that perforin is not essential in the cell‐mediated acute rejection of a fully mismatched heart allograft. However, perforin‐dependent effector mechanisms appeared to be limiting in the T cellmediated rejection of heart allografts differing only at a single major histocompatibility complex class I antigen (bm1), because these grafts survived longer (mean 87.8 days) in perforin‐deficient than in control mice (mean 31.5 days).