Acute rejection of vascular heart allografts by perforin-deficient mice.
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 cell-mediated 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).
Schulz
M
M
Sandoz Pharma Ltd., Basel, Switzerland.
Schuurman
H J
HJ
Joergensen
J
J
Steiner
C
C
Meerloo
T
T
Kägi
D
D
Hengartner
H
H
Zinkernagel
R M
RM
Schreier
M H
MH
Bürki
K
K
D000818:Animals; D000954:Antigens, Surface / Q000502:physiology; D003602:Cytotoxicity, Immunologic; D006084:Graft Rejection; D016027:Heart Transplantation / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000473:pathology; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014184:Transplantation, Homologous; D019014:fas Receptor
D000954:Antigens, Surface; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D019014:fas Receptor; D054353:Perforin