At present, suppression of the immune response is the most efficacious therapy in most autoimmune diseases, in the control of transplant rejection, and in other situations in which the immune system plays a significant pathogenic role. Most of the currently used im-munosuppressive drugs have a generalized, nonspecific suppressive effect. Some im-munosuppressants have effects practically limited to either humoral or cell-mediated im-munity, but they still lead to generalized immunosuppression. More recently, a variety of new biological agents have been tried in different immunosuppressive regimens, including monoclonal antibodies to T cells and their subsets, immunotoxins, IL-2–toxin conjugates, anti-idiotypic antibodies, etc., with the goal of developing more specific and effective ther-apies. In many cases these agents are still in the early stages of evaluation, and it is too soon to issue definite judgments about their usefulness. It is, how-ever, unquestionable that they are the prototypes of approaches that will be more and more used in the near future.
A variety of drugs, ranging from glucocorticoids to cytotoxic drugs, have been used for the purpose of suppressing undesirable immune responses. While many of these drugs are loosely termed “immunosuppressive,” they differ widely in their mechanisms of action, toxicity, and efficacy. The exact mechanisms of action of immunosuppressive drugs are difficult to determine, partly because the physiology of the immune response has not yet been completely elucidated. The targets of immunosuppressive therapies are rather diverse and, depending on the agents, may include phagocytosis and antigen-processing by macrophages; antigen recognition by lymphocytes; proliferation and/or differentiation of lymphocytes; production of cytokines; immune effector mechanisms, including the pro-duction and release of cytotoxic leukocytes, antibodies, and/or delayed hypersensitivity mediators.