Triptolide suppresses T-lymphocyte proliferation by inhibiting interleukin-2 receptor expression, but spares interleukin-2 production and mRNA expression.

The purpose of this study was to elucidate the mechanism of action of triptolide on the T-lymphocyte-mediated immune response. Lymphocytes were incubated with a suboptimal dose of Con A or PHA in the presence or absence of varying doses of triptolide to assess the effect of triptolide on lymphocyte proliferation, interleukin-2 (IL-2) production and IL-2 receptor expression. Then, Con A or PHA induced T-blast cells were cultured with a sufficient dose of recombinant human IL-2 in the presence or absence of triptolide to evaluate the effect of triptolide on the interaction of IL-2 and IL-2 receptors. The effect of triptolide on the immune response in vivo was also investigated. The results of these studies clearly demonstrated that triptolide selectively inhibited the T-lymphocyte proliferative response to Con A and PHA, but had less effect on LPS-induced B-lymphocyte proliferation. Triptolide also suppressed the expression of IL-2 receptors on PHA induced T-blast cells, but did not alter the production of IL-2 by mouse splenic cells and human tonsil lymphocytes. Furthermore, the results also showed that triptolide at higher concentration had a slight inhibitory effect on the interaction of IL-2 and IL-2 receptors, and addition of exogenous IL-2 did not reverse the inhibiting action of triptolide on T-cell proliferation. Taken together, these results suggest that triptolide inhibits T-lymphocyte proliferation mainly by affecting IL-2 receptor expression rather than IL-2 production.