Recurrence of acute rejection in the absence of CD3-positive lymphocytes

Allograft rejection is the single largest impediment to successful transplantation. Therapy targeted to lymphocytes has been in practice for many years using polyclonal heteroantisera. These products are generally accepted as being useful for the prevention and treatment of rejection; however, there have been problems with specificity, lot to lot variability, and supply. Therapy with monoclonal antibodies such as OKT3 may circumvent these problems and may allow for refined specificity. OKT3 has been shown to be highly effective at reversing acute renal allograft rejection. The few treatment failures were attributed to anti-mouse antibodies eliminating the OKT3, or to delay of therapy to such a late stage that rejection was irreversible. We present two cases which demonstrate successful reversal of acute rejection in cadaveric renal transplants by OKT3. The reversal was transient, however, in both cases, as both patients experienced recurrence of rejection while still receiving the monoclonal antibody. This occurred despite the absence of CD3-positive cells in the peripheral blood, and the presence of excess OKT3 in the serum. This implies that CD3-negative lymphocytes may under certain circumstances contribute to the rejection phenomenon.