Better-surviving liver grafts by the injection of anti-CD2 antibody: the important roles of host CD8+ and CD2+CD28+ T cells in chronic graft rejection and beta type platelet-derived growth factor receptor (PDGFR-beta) expression on apoptotic liver grafts.
Syngeneic liver grafts were implanted in the livers of 22 LEW/Sea strain rats. To prolong the graft survival, anti-CD2 monoclonal antibody (MAb) or anti beta type platelet-derived growth factor receptor (PDGFR-beta) antibody (Ab) was injected, or splenectomy was performed in the rats which were then followed until 10 to 11 weeks posttransplantation. The 22 rats with chronic graft rejection showed increased CD8a-like antigen (probably Fas ligand) on the peripheral blood T cells. All the liver grafts had both necrosis and apoptosis. The liver graft apoptosis was indicated by histopathological abnormalities, and by DNA strand breaks and hemosiderin depositions in the cytoplasm. PDGFR-beta expression in the apoptotic liver graft was demonstrated immunohistochemically. Among the 17 rats injected with anti-CD2 MAb, CD2 signaling on host T cells was effectively suppressed by the injection of anti-CD2 MAb in 4 rats with better-surviving liver grafts. In these 4 rats, CD28 antigen on thymic lymphocytes was down-modulated and high numbers (136-233-positive cells per lobe) of the epithelial reticular cells with apoptotic lymphocytes were counted. Anti-PDGFR-beta Ab caused high pulmonary secretions of growth factors and reticular fibrosis in the lungs of 5 rats injected with the Ab. Anti-PDGFR-beta Ab injection reduced the host cell apoptosis in the lung and thymus, but did not prolong the survival of liver grafts. In the 9 rats with both splenectomy and anti-CD2 MAb injection, pulmonary apoptosis was induced with the 6-16% reductions of CD4+ lymphocytes. Prolonged graft survival was observed in only one of the 9 rats. Anti-CD2 MAb was effective for prolonging the liver graft survival with suppressed CD28 antigen, but anti-PDGFR-beta Ab and splenectomy were not.
Nakatsuji
T
T
Department of Transfusion, Hamamatsu University School of Medicine, Japan. nh80415@hama-med.ac.jp
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D017209:Apoptosis / Q000276:immunology; D018801:CD2 Antigens / Q000276:immunology*; D018106:CD28 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000187:drug effects* / Q000276:immunology*; D016031:Liver Transplantation; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor / Q000276:immunology*; D014181:Transplantation Immunology; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D018801:CD2 Antigens; D018106:CD28 Antigens; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor