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.