ACUTE REJECTION OF VASCULAR HEART ALLOGRAFTS BY PERFORIN-DEFICIENT MICE

To study the role of perforin in cell-mediated graft rejection, vascul arized hearts were grafted to perforin-deficient C57BL/6 and control C 57BL/6 recipient mice. Fully allogeneic heart grafts (BALB/c) were acu tely rejected by both recipients within 6 days. Peritoneal exudate lym phocytes from control mice but not from perforin-deficient mice exhibi t a strong alloreactive cytotoxic activity in vitro. Histological anal ysis of the rejected tissues demonstrated extensive mononuclear cell i nfiltrates in both recipients. Flow cytometry analysis and immunohisto logy of graft-infiltrating cells showed similar proportions of lymphoc yte subsets (CD8 much greater than CD4). Collectively, these data indi cate that perforin is not essential in the cell-mediated acute rejecti on of a fully mismatched heart allograft. However, perforin-dependent effector mechanisms appeared to be limiting in the T cell-mediated rej ection of heart allografts differing only at a single major histocompa tibility complex class I antigen (bm1), because these grafts survived longer (mean 87.8 days) in perforin-deficient than in control mice (me an 31.5 days).