Progress in immunosuppressive drugs during the past decade has been phenomenal. The experimentalists and clinicians have at their disposal a whole battery of drugs, including prednisone, 6-mercaptopurine, azathioprine, methotrexate, and cyclophosphamide. However, newer drugs with higher therapeutic ratios are needed, the mechanisms of action of the outstanding drugs need to be resolved at the cellular and intracellular level, and better methods are needed to restrict the action of drugs to the immunocompetent precursor cells that are responsive only to the test antigen. Fulfillment of these demands will require the concerted efforts of imaginative specialists from several disciplines, including biochemistry, pharmacology, genetics, medicine, and immunology.
The consensus on the cellular mechanism of immune response and induction of immunological tolerance was discussed briefly before the general discussion on the suppressive and enhancing effects of immunosuppressive drugs. The reason for taking this approach was to emphasize that, although the cellular and biochemical events of an immune response are complex, the major pathways are now known (see fig. 1). This might allow the readers to make guesses as to where the sites of action of the various drugs are and to formulate more definitive experiments. It is hoped that future investigators will include, among their techniques, model systems that will enable them to deduce the suppressive and stimulatory effects of drugs and other agents on antigen-reactive immunocompetent cells, immunocompetent precursors of terminal effector cells, immature and mature effector cells, phagocytes, cells engaged in complement formation, and cells involved in the inflammatory events associated with immediate and delayed hypersensitivities. Thus, for example, in dealing with the mechanism of action of drugs on the precursors of terminal effector cells, one would like to know how a drug can affect their receptors for antigen-reactive cells and "processed antigens," their capacity to change from resting to proliferating cells, and their capacity to differentiate into functional effector cells.
At the present rate of progress it is conceivable that within the next decade the problem of immunosuppression may be practically solved to the extent that routine, simple methods may be available to rapidly induce and terminate tolerance to a limited number of antigens without causing serious damage to the immunological and other vital tissues of the recipient.
- 1970 by The Williams & Wilkins Co.