Mechanism of immunosuppression of the antirheumatic herb TWHf in human T cells

Objective. To investigate the immunosuppressive mechanism of Tripterygium w ilfordii Hook-F (TWHf) in human T cells, TWHf, a traditional Chinese medici nal herb for rheumatoid arthritis, has been shown to inhibit the function o f immune effector cells such as neutrophils, macrophages, and B lymphocytes , Methods. T cell survival was evaluated with trypan blue exclusion assay, mo rphologic changes with Wright's stain, the induction of endonuclease activi ty with DNA fragmentation assay, and the subdiploid DNA content with flow c ytometry. T cell activation was measured with interleukin 2 (IL-7) ELISA an d the expression of several surface molecules with flow cytometry. Results. At high dosages, TWHf caused inhibition of T cell proliferation an d this mechanism was mediated through the induction of apoptosis. TWHf, in noncytotoxic dosages, was as potent as cyclosporin A and more potent than p rednisolone and cyclophosphamide in inhibiting IL-2 production from activat ed T cells. TWHf also inhibited both phorbol 12-myristate 13-acetate induce d IL-2R alpha expression and ionomycin induced CD40 ligand expression. TWHf did not reverse downregulated expression of CD3 and CD4 by phorbol ester s timulation. Conclusion. This is the first evidence that the immunosuppressive mechanism of TWHf in T cells was mediated through both downregulation of T cell rece ptor signaling pathway and induction of cellular apoptosis, which is defect ive in autoimmune diseases.