Interleukin 2 receptor--a target for immunosuppressive therapy.

Abstract

Despite the relative effectiveness of standard immunosuppressive therapy in clinical transplantation, rejection is still primarily responsible for deterioration or complete loss of allograft function. Treatment of rejection mandates additional immunosuppression, most frequently high-dose steroids or polyclonal antilymphocyte globulins. These powerful modalities, however, although often effective, may produce serious complications. Thus, while the results of clinical transplantation have improved progressively during the last few decades, more specific drugs and novel therapeutic strategies are still needed which will either replace the presently used agents or allow their administration in markedly reduced dosages. The goal of donor-specific immunosuppression and the creation of host tolerance to a foreign graft are still elusive. Hopes have been raised by recent advances in hybridoma technology to produce effective and reproducible biological suppression with monoclonal antibodies (mAbs) against various lymphocyte populations. Indeed, mAbs directed against T cells or T-cell subsets have been shown to be potent immunosuppressive agents both experimentally and clinically. 1-4 However, the use of mAbs broadly reactive with differentiation antigens on T lymphocytes does not solve the problem of side effects caused by general immunosuppression. An ideal therapeutic agent should target only those lymphocytes that are specifically alloreactive against the foreign graft without affecting physiological host immune surveillance and normal defense mechanisms. Such specific immunosuppression could be based upon the inhibition and/or elimination of antigen-activated T-cell clones without affecting the pool of resting lymphocytes. Activation of T lymphocytes by antigen leads to a number of sequential changes in their surface components, including induction of cell surface molecules that are absent or only weakly expressed in the resting state.5•6 One of these activation