Trichostatin A inhibits the activation of CD(4)(+) T cells by suppressing CD(28) expression in mice / 南方医科大学学报

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the mechanism of trichostatin A(TSA), a histone deacetylase (HDAC) inhibitor, in inhibiting the activation of CD(4)(+) T cells in mice.</p><p><b>METHODS</b>The CD(4)(+) T cells isolated from the spleen of C57BL mice were treated with different concentrations of TSA (2, 20, and 200 nmol/L) for 24 h, and CD(3), CD(28) and interleukin-2 (IL-2) mRNA levels were measured with reverse transcription-polymerase chain reaction. The protein expressions of CD(3), CD(28) and IL-2 were measured by fluorescence-activated cell sorting and ELISA analysis. ZAP70 and PI3K protein expression in CD(4)(+) T cells activated by CD(3) and CD(28) monoclonal antibody were analyzed by Western blotting.</p><p><b>RESULTS</b>TSA dose-dependently inhibited the transcription and protein expression of CD28 in CD(4)(+) T cells and reduced the expression of PI3K protein in activated CD(4)(+) T cells, without showing significant effect on the expression of ZAP70. TSA treatment of the cells also resulted in significantly decreased mRNA and protein expressions of IL-2 (P<0.01).</p><p><b>CONCLUSION</b>TSA can regulate the immunological activity of CD(4)(+) T cells by inducing mRNA and protein expressions of CD(28), which inhibits the activation of the co-stimulatory signal transduction in CD(4)(+) T cells and decreases the secretion of IL-2.</p>