Evidence that genistein, a protein-tyrosine kinase inhibitor,
inhibits CD28 monoclonal-antibody-stimulated human T cell
proliferation
Atluru S, Atluru D
Transplantation 1991 Feb 51:2 448-50
Abstract
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.
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