An increased number of cell subpopulations recognized in the immune system has led to better understanding of its diverse biological functions. B lymphocytes were differentiated from T lymphocytes (1), then the latter population was divided further into T helper/inducer (Th) and T cytotoxic/suppressor (Tc/s) subsets (2). In addition, the introduction of the cell hybridization technique by Köhler and Milstein (3, 4) allowed production of continuous cell lines secreting monoclonal antibodies of predefined specificity, which in turn allowed various distinct lymphocyte membrane molecules to be characterized (5). Mabs have become one of the most vital tools in broadening appreciation of the complexity of the immune system itself, and are also becoming increasingly important as therapeutic agents. For instance, OKT3, a mAb directed against the pan–T cell (CD3) antigen, has been successfully used to prevent and/or reverse ongoing rejection episodes in clinical organ transplantation (6, 7). Anti-interleukin-2 receptor (CD25) mAbs (33B3. 1, anti-Tac, YTH-906, BT 563) have been em-ployed prophylactically as adjunctive therapy in several centers (8–11). Recently, the demonstration of immunosuppressive/immunomodulatory effects of CD4 mAbs in a variety of experimental transplantation models has prompted early trials of these reagents in man (12). The purpose of this overview is to summarize findings of the effects of CD4 mAbs in organ allograft recipients, to discuss the mechanisms by which they may influence host responsiveness against foreign tissue, and to outline prospects for CD4 mAbs in the immunosuppressive armamentarium.

Expression and Morphology of CD4 Cell Surface Antigen The CD4 antigen (T4/Leu3 in human, L3T4 in mouse, W3/25 in rat) is a member of the immunoglobulin gene superfamily, originally identified in the mouse as Lyt 1", 2T3T (2). It is expressed on subpopulations of mature peripheral T lymphocytes and the majority of immature thymocytes in humans,