Suppression of T cell functions by hydroxamic acid-based histone deacetylase inhibitors.
ABSTRACT Histone deacetylase inhibitors (HDACis) have recently been shown to suppress inflammatory responses at much lower concentrations than that the concentrations that produce an antitumor effect. In the current study, the inhibitory activity of T cell functions by three different HDACis was compared, and the mechanisms underlying the inhibitory activity were demonstrated. Trichostatin-A (TSA) and scriptaid (ST) had potent inhibitory effects on the proliferation of T cells. TSA suppressed the synthesis of the T cell-activating cytokine, interleukin (IL)-2, and the T cell-derived cytokines, interferon (IFN)-γ, IL-4, and IL-13. In addition, TSA induced inhibition of cell cycle progression and IL-2 receptor expression. On the whole, TSA had a stronger effect on T cell functions than other HDACis. Similarly, a longer duration of hyperacetylation was observed in the cells that had been exposed to TSA. Thus, the inhibition of histone deacetylation appears to be related to the inhibitory effect of TSA. These results are expected to serve as a guide for future studies on the ability of HDACis to inhibit acute and chronic inflammatory diseases provoked by T cells.