SELECTIVE IN-VIVO DELETION OF ALLOACTIVATED TH1 CELLS BY OKT3 MONOCLONAL-ANTIBODY IN ACUTE REJECTION

The OKT3 monoclonal antibody (mAb) recognizing the CD3 complex on huma n T-cells has been shown to be an effective immunosuppressive agent fo r the treatment and the prevention of acute rejection episodes in allo graft recipients [1]. Following the initial doses of OKT3 mAb, activat ion of T lymphocytes and monocytes is observed. This is accompanied by a massive cytokine release, particularly following the first injectio n. The mAb opsonizes the circulating T-cells and the coated cells disa ppear quickly from circulation. OKT3 mAb is commonly administered for 5-10 days. The manifestation of side effects weeks (cytomegalovirus in fection/disease, bacterial and fungal infections) or even months (Epst ein-Barr-Virus related lymphoproliferative disease) after therapy as w ell as the good long-term effects on graft function suggest long-lasti ng immunosuppressive effects. Since peripheral T-cells reappear in the circulation already during therapy (with modulated CD3/T-cell recepto r complex) and T-cell counts reach commonly pretreatment levels within 2-3 days after cessation of OKT3 mAb, the long-lasting immunosuppress ive effects are not simply explainable by T-cell depletion. We wondere d whether T-cells reappearing in the circulation after cessation of th erapy, were functionally different from those before OKT3 mAb therapy. Our data suggest a selective depletion of activated T-cells particula rly of type I-like T-cells by OKT3 mAb resulting in long-lasting immun e deviation that may explain the long-term effects of OKT3 mAb treatme nt. (C) 1997 Elsevier Science B.V.