Monitoring immunosuppression following renal transplantation

Renal allograft recipients were given azathioprine and prednisone for immunosuppression following transplantation. In addition, pulses of steroids or courses of treatment with antithymocyte globulin (ATG) or PAN.OKT3 were employed to combat acute rejection episodes. Our results support the concept that ATG and PAN.OKT3 are useful in the treatment of acute kidney allograft rejection. In our experience, ATG often reversed acute kidney allograft rejection episodes and then provided relatively long-lasting immunosuppression with stable graft function. In contrast, PAN.OKT3 was more effective in reversing acute rejection, but subsequent rejection episodes occurred more frequently. In patients treated with PAN.OKT3, cells reacting with OKT3, OKT4 and OKT8 were removed from the circulation within minutes following the initial treatment, and the levels of these cells remained dramatically depressed during the first few days of treatment. Subsequently, peripheral blood cells which reacted with OKT4 or OKT8, but not OKT3, could be detected in most patients, even though treatment continued and excess circulating PAN.-OKT3 was present. Experiments in which these cells were cultured for 24 or 72 hr indicated that antigenic modulation by OKT3 had occurred in vivo. These results raise interesting questions about the mode of action of PAN.OKT3, and suggest that the combination of PAN.OKT3 with an agent which can establish long-lasting immunosuppression may be more effective than either agent given alone.