OKT4 AND OKT4A ANTIBODY TREATMENT AS IMMUNOSUPPRESSION FOR KIDNEY TRANSPLANTATION IN RHESUS MONKEYS

Abstract

A mixture of OKT4 + 4A monoclonal antibodies (reactive with T4 cells) was tested for its immunosuppressive potential in rhesus monkeys receiving a kidney allograft. The kidney transplant model used in this study was designed to mimic the clinical situation. All animals received a low dose of azathioprine and prednisolone and the effectiveness of monoclonal antibody treatment was assessed in nontransfused and transfused recipients. The treatment very effectively suppressed acute graft rejection in untransfused recipients. In transfused recipients, which show an improved graft survival, no additional favorable effect of OKT4 + 4A treatment was seen when this treatment was given at the time of transplantation. Transfused recipients that reject their kidney in an acute fashion apparently do not benefit from the OKT4 + 4A treatment because they have generated primed effector cells that belong to a T4-negative subpopulation or a T4-positive subpopulation with high affinity for donor cells. When the OKT4 + 4A treatment was given at the time of graft rejection in transfused recipients, treating chronic rather than acute rejection, a modest improvement in graft survival was observed. Anti-T4 antibodies will be of limited value for clinical transplantation and should be used in combination with other immunosuppressive drugs.