Promotion of murine orthotopic corneal allograft survival by systemic administration of anti-CD4 monoclonal antibody.
A mouse model of orthotopic corneal allograft rejection was used to examine the efficacy of anti-CD4 and anti-CD8 monoclonal antibodies in preventing immunologic rejection of corneal allografts. Although it is believed by many that corneal graft rejection is mediated, at least in part, by CD8-positive cytotoxic T-lymphocytes, systemic administration of anti-CD8 antibody did not reduce the rejection rate of corneal allografts that differed from the host at the entire major histocompatibility complex. By contrast, systemic administration of anti-CD4 monoclonal antibody reduced the rejection rate from 83% (untreated controls) to 33%. Fluorocytometric analysis of residual lymphoid populations showed that neither monoclonal antibody eliminated the inappropriate subset of T-cells in antibody-treated animals. In vitro cell-mediated cytotoxicity assays showed that both antibodies eliminated allospecific cytotoxic T-lymphocyte populations; however, only anti-CD4 antibody promoted graft survival. Thus, these results indicate that anti-CD4 monoclonal antibody is a powerful immunosuppressive agent for promoting corneal graft survival and that CD8-positive T-cells alone do not cause rejection of corneal allografts.
Department of Ophthalmology, University of Texas Southwestern Medical Center 75235.
Y G
YG
He
J
J
Ross
J Y
JY
Niederkorn
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D006085:Graft Survival / Q000276:immunology*; D015948:Keratoplasty, Penetrating / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016176:T-Lymphocyte Subsets / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal