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- 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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