New strategies in immunosuppression

This article reviews recent papers relating to immunosuppressives and attempts to categorise the bewildering number of new reagents according to their effects on the immune response. It is apparent that the majority of groups are concentrating on reagents which, like cyclosporin A, are predominantly directed at T cells (42% of the last 200 papers inTransplantation, Transplant International andTransplantation Proceedings). The major change in strategy which is occurring relates to the rapidly increasing use of reagents directed against T cell subsets, especially those directed against the interleukin-2 receptor and CD4-positive T cells. This groups's share of the market has risen from 2% to over 12% within 5 years. New successful monoclonal antibodies include reagents directed against antigen-presenting cells and against molecules directly involved in cell adherence. The use of donor bone marrow or subsets of cells from donor bone marrow as inducers of non-reactivity, especially to solid organ grafts, is certainly one of the most exciting of the non-antibody protocols. It is encouraging that relatively specific immunosuppression can be induced in animals by combinations of specific and non-specific reagents as well as by specific reagents alone. This will facilitate the introduction of specific protocols into the human situation, and this strategy holds out great hope for the future. Unfortunately, one of the most effective ingredients of such combination therapies in animal models (anti-CD4) appears to have its tolerogenic potential abrogated by cyclosporin A and FK-506. One area of immunosuppression which is receiving scant interest relates to antibody (especially non human leucocyte antigen antibody) production, but as the interest in xenotransplantation increases it is anticipated that major new interest will emerge in this area.