Evidence that genistein, a protein-tyrosine kinase inhibitor, inhibits CD28 monoclonal-antibody-stimulated human T cell proliferation.
In the present investigation, we compared the immunosuppressive effects of genistein and CsA on anti-CD28 stimulated human T cell proliferation, IL-2 production, and IL-2R expression. Genistein, an isoflavanoid compound, is a specific protein tyrosine kinase inhibitor and inhibited the PMA plus anti-CD28 stimulated T cell proliferation. In contrast, proliferation of T cells stimulated with PMA plus anti-CD28 is resistant to the inhibitory effects of CsA. Similar results were obtained with IL-2 synthesis and IL-2R expression. PHA plus anti-CD28 or PMA plus anti-CD28-induced IL-2 synthesis was inhibited by genistein, and CsA, though it inhibited the PHA plus PMA-stimulated IL-2 synthesis, failed to have any effect on PMA plus anti-CD28-induced IL-2 synthesis. Genistein at the concentration that inhibited T cell proliferation and IL-2 synthesis also showed significant inhibitory effects on PMA plus anti-CD28 stimulated IL-2R expression while CsA had no effect on IL-2R from these cultures. Our data suggest that genistein is a powerful immunosuppressive agent, with no toxic effects on T cells, and has the potential for use in the prophylaxis and treatment of allograft rejection. Since genistein blocks the CsA-resistant pathway of T cell proliferation, the combined usage of these two agents may provide better immunosuppressive effect and a lesser degree of CsA-induced nephrotoxicity.
Atluru
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Department of Anatomy and Physiology, Kansas State University, Manhattan 66506.
Atluru
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D015703:Antigens, CD / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D018106:CD28 Antigens; D002470:Cell Survival / Q000187:drug effects; D003524:Cyclosporins / Q000494:pharmacology; D019833:Genistein; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000096:biosynthesis; D007529:Isoflavones / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D015375:Receptors, Interleukin-2 / Q000378:metabolism
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D003524:Cyclosporins; D007376:Interleukin-2; D007529:Isoflavones; D015375:Receptors, Interleukin-2; D019833:Genistein; D011505:Protein-Tyrosine Kinases