Lymphocyte function in patients treated with monoclonal anti-T3 antibody for acute cadaveric renal allograft...

We are participating in a multicenter trial testing the efficacy of a murine monoclonal antihuman peripheral T lymphocyte antibody (OKT3.PAN) as immunosuppressive therapy for the treatment of acute cadaveric renal allograft rejection. Although clinical data indicate that administration of this antibody clears the circulating lymphocyte pool of T3-positive cells, some in vitro studies have called into question whether the antibody is indeed lymphocytotoxic. Other in vitro data suggest that the antibody is a potent mitogen. To address these problems and investigate the effect of the antibody on T cell function, we have studied spontaneous blastogenesis, response to the lectins phytohemagglutinin (PHA) and concanavalin A (ConA), and response to donor-specific and non-donor-specific alloantigen in a one-way MLC in 9 patients treated with anti-T3 for acute rejection and 9 steroid-treated controls. Patients cells were harvested with standard techniques and studied after transplantation, but prior to acute rejection, on days 3 and 12 of therapy and 1 week after cessation of therapy. All patients received baseline immunosuppression with azathioprine and steroids. Acute rejection was reversed with alpha T3 antibody (5 mg i.v./day-1 X 14 days) in 8 of 9 patients and in 6 of 9 steroid-treated controls. Spontaneous blastogenesis was not enhanced by anti-T3 nor did it rise during therapy. PHA and Con A responsiveness were dramatically and significantly depressed by therapy with anti-T3 or steroids on days 3 and 12. Although PHA responsiveness rebounded past baseline 1 week after monoclonal therapy, it was depressed compared with the steroid-treated patients. On the other hand, Con A responsiveness was still significantly depressed one week after monoclonal therapy compared with prerejection values or with controls. Response to donor-specific and to non-donor-specific alloantigen was significantly depressed with anti-T3 therapy compared with steroid controls, and it did not rise during therapy. Donor-specific responses tended to be slower in returning to pretreatment values in the OKT3 patients compared with steroid controls. In summary: (1) Anti-T3 antibody did not enhance spontaneous blastogenesis in patients treated for acute rejection; (2) Con A and PHA responses were dramatically depressed by anti-T3 therapy and returned to baseline following different time courses; (3) Non-donor-specific alloresponse and, more important, donor-specific alloresponse, was more depressed--and for longer periods--by anti-T3 than by conventional steroid anti-rejection therapy.(ABSTRACT TRUNCATED AT 400 WORDS)