Yang S X, Xie S S, Gao H L, Ma D L, Long Z Z
Department of Immunology, Beijing Medical University, People's Republic of China.
Int J Immunopharmacol. 1994 Nov;16(11):895-904. doi: 10.1016/0192-0561(94)90044-2.
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.
本研究的目的是阐明雷公藤甲素对T淋巴细胞介导的免疫反应的作用机制。在存在或不存在不同剂量雷公藤甲素的情况下，将淋巴细胞与次优剂量的刀豆蛋白A（Con A）或植物血凝素（PHA）一起孵育，以评估雷公藤甲素对淋巴细胞增殖、白细胞介素-2（IL-2）产生和IL-2受体表达的影响。然后，在存在或不存在雷公藤甲素的情况下，将Con A或PHA诱导的T母细胞与足量的重组人IL-2一起培养，以评估雷公藤甲素对IL-2和IL-2受体相互作用的影响。还研究了雷公藤甲素对体内免疫反应的影响。这些研究结果清楚地表明，雷公藤甲素选择性抑制T淋巴细胞对Con A和PHA的增殖反应，但对脂多糖（LPS）诱导的B淋巴细胞增殖影响较小。雷公藤甲素还抑制PHA诱导的T母细胞上IL-2受体的表达，但不改变小鼠脾细胞和人扁桃体淋巴细胞产生IL-2的情况。此外，结果还表明，较高浓度的雷公藤甲素对IL-2和IL-2受体的相互作用有轻微抑制作用，添加外源性IL-2并不能逆转雷公藤甲素对T细胞增殖的抑制作用。综上所述，这些结果表明雷公藤甲素主要通过影响IL-2受体表达而非IL-2产生来抑制T淋巴细胞增殖。
