TRIPTOLIDE SUPPRESSES T-LYMPHOCYTE PROLIFERATION BY INHIBITING INTERLEUKIN-2 RECEPTOR EXPRESSION, BUT SPARES INTERLEUKIN-2 PRODUCTION AND MESSENGER-RNA EXPRESSION

The purpose of this study was to elucidate the mechanism of action of triptolide on the T-lymphocyte-mediated immune response. lymphocytes w ere incubated With a suboptimal dose of Con A or PHA in the presence o r absence of varying doses of triptolide to assess the effect of tript olide on lymphocyte proliferation, interleukin-2 (IL-2) production and IL-2 receptor expression. Then, Con A or PHA induced T-blast cells we re cultured with a sufficient dose of recombinant human IL-2 in the pr esence or absence of triptolide to evaluate the effect of triptolide o n 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 inhibit ed the T-lymphocyte proliferative response to Con A and PHA, but had l ess effect on LPS-induced B-lymphocyte proliferation. Triptolide also suppressed the expression of IL-2 receptors on PHA induced T-blast cel ls, but;did not alter the production of IL-2 by mouse splenic cells an d human tonsil lymphocytes. Furthermore, the results also showed that triptolide at higher concentration bad a slight inhibitory effect on t he interaction of IL-2 and IL-2 receptors, and addition of exogenous I L-2 did not reverse the inhibiting action of triptolide on T-cell prol iferation. Taken together, these results suggest that triptolide inhib its T-lymphocyte proliferation mainly by affecting IL-2 receptor expre ssion rather than IL-2 production.