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Regulation of lymphocyte growth by antagonists of interleukin-2 or its cellular receptor
1Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia.
The dependence of T cell proliferation on the production, binding and utilization of the lymphokine growth factor IL-2 has fostered the development and testing of new classes of drugs which act to either inhibit IL-2 production or the interaction of IL-2 with its cellular receptor. We have reviewed evidence which documents the potent immunosuppressive effects of inhibitors of IL-2 synthesis and secretion, such as Ciclosporin A, and of anti-IL-2 receptor MAb. The similarities of the potency and specificity of these agents and their effectiveness in a wide range of clinical settings encourage further studies on their mechanism of action. Perhaps the most dramatic similarity is the induction of long-term nonresponsiveness after drug removal to antigens present at the time of drug therapy. This observation has profound importance both on clinical manipulation with these agents and n the origins and maintenance of self-tolerance.
The dependence of T cell proliferation on the production, binding and utilization of the lymphokine growth factor IL-2 has fostered the development and testing of new classes of drugs which act to either inhibit IL-2 production or the interaction of IL-2 with its cellular receptor. We have reviewed evidence which documents the potent immunosuppressive effects of inhibitors of IL-2 synthesis and secretion, such as Ciclosporin A, and of anti-IL-2 receptor MAb. The similarities of the potency and specificity of these agents and their effectiveness in a wide range of clinical settings encourage further studies on their mechanism of action. Perhaps the most dramatic similarity is the induction of long-term nonresponsiveness after drug removal to antigens present at the time of drug therapy. This observation has profound importance both on clinical manipulation with these agents and n the origins and maintenance of self-tolerance.