Discovery of novel immunosuppressants in vitro

Treatment with immunosuppressants has opened today possibilities of clinical organ transplantation. Allograft rejection is mainly mediated by activated lymphocytes. Simple in vitro models are available to detect new drugs with immunosuppressant activity. Peripheral blood lymphocytes are activated by antigens or mitogens and cultures in the presence or absence of test compounds. The endpoints of these cultures include cell proliferation, gene activation (mRNA) and protein expression. These methods allow the identification of novel immunosuppressants, and the determination of the mode of action, e.g. inhibitors of transcription, (cyclosporine and FK 506) or inhibitors of lymphokine signal transduction (rapamycin).