We describe the first clinical trial of
OKT3, a monoclonal
anti-T-cell antibody, for prevention of kidney transplant rejection. 13 patients receiving a first cadaveric kidney transplant were randomly assigned to conventional treatment with
azathioprine and high-dose
steroids (7 patients) or to treatment with daily injection of
OKT3 alone (6 patients). The first
OKT3 injection resulted in a dramatic decrease in T3+, T4+, and T8+ cells, while patients simultaneously experienced
fever,
chills, and
diarrhea. These symptoms did not recur with subsequent
injections. All six OKT3-treated patients had a rejection necessitating introduction of
steroids 12.8 +/- 2.9 days after surgery. Rejection was related to appearance of anti-OKT3
antibodies leading to disappearance of detectable
OKT3 in the serum. Modulating (T3-, T4+ or T3-, T8+) cells were observed in all patients but were functionally inactive. As no rejection was observed before day 9 posttransplant, despite the lack of additional
immunosuppressive agents, we conclude that
OKT3 is a powerful, well-tolerated
immunosuppressive agent. However, it is highly immunogenic and anti-OKT3
antibodies lead to loss of clinical effectiveness in this protocol. The use of
OKT3 alone for prevention of kidney graft rejection cannot be recommended until a method for reducing the effects of anti-OKT3 immunization is developed.