Frontiers in immunosuppression

Immunosuppressive therapy has relied on tailoring combinations of relatively nonselective drugs to individual patient tolerance. The next steps in the development of small molecule agents are to define and to develop selective inhibitors of cascades unique to T cells. This selectivity would minimize the inherent toxicity associated with drug therapy. Two targets identified at present are lymphoid cell kinase (lck; Signal 1) and Janus kinase 3 (Jak3; Signal 3). Although preliminary data support the immunosuppressive efficacy of putative antagonists, it is not clear that they are sufficiently selective for the target molecule as opposed to other kinases. Another novel approach to immunosuppression seeks to promote lymphoid cell sequestration in nodes through agonistic effects on sphingosine-1-phosphate receptors. Due to the availability of specific assays and high through put analysis of molecular candidates, the next decade should witness a panoply of new agents.