Matsui K
Department of Microbiology, Meiji College of Pharmacy, Tokyo, Japan.
FEMS Immunol Med Microbiol. 1996 Jun;14(2-3):121-7. doi: 10.1111/j.1574-695X.1996.tb00278.x.
In previous study, we observed that the purified substance Salmonella typhimurium-derived inhibitor of T-cell proliferation (STI) had an immunosuppressive effect, demonstrated as the suppression of mitogenic lectin-induced proliferation of murine spleen cells. In the present study, we confirmed the immunosuppressive effect of STI, which suppressed the proliferation of murine splenic T-lymphocytes activated with the anti-CD3 antibody (Ab) and phorbol 12-myristate-13 acetate (PMA) and this phenomenon was accompanied by augmentation of interferon-gamma (IFN-gamma) secretion and inhibition of interleukin-2 (IL-2) secretion. Furthermore, the augmentation of IFN-gamma secretion caused IL-2 receptor alpha chain (IL-2R alpha) over expression on T-cells. However, the addition of an anti-IFN-gamma Ab and recombinant IL-2 (rIL-2) did not reverse the suppressed T-cell proliferation, although the level of IL-2R alpha expression on T-cells recovered to around normal. Furthermore, Western blotting using an anti-phosphotyrosine Ab showed that IL-2R-mediated tyrosine phosphorylation of protein substrates in T-cells was inhibited by incubation with STI for 48 h and this inhibition was not reversed by adding the anti-IFN-gamma Ab and rIL-2. These results suggest that STI-induced suppression of T-cell proliferation involves a defect in IL-2R function and/or IL-2 signaling pathway in T-cells.
在先前的研究中,我们观察到纯化的鼠伤寒沙门氏菌衍生的T细胞增殖抑制剂(STI)具有免疫抑制作用,表现为对促有丝分裂凝集素诱导的小鼠脾细胞增殖的抑制。在本研究中,我们证实了STI的免疫抑制作用,它抑制了用抗CD3抗体(Ab)和佛波醇12-肉豆蔻酸酯-13-乙酸酯(PMA)激活的小鼠脾T淋巴细胞的增殖,并且这种现象伴随着干扰素-γ(IFN-γ)分泌的增加和白细胞介素-2(IL-2)分泌的抑制。此外,IFN-γ分泌的增加导致T细胞上IL-2受体α链(IL-2Rα)的过度表达。然而, 添加抗IFN-γ抗体和重组IL-2(rIL-2)并没有逆转被抑制的T细胞增殖,尽管T细胞上IL-2Rα的表达水平恢复到了正常水平左右。此外,使用抗磷酸酪氨酸抗体的蛋白质印迹法显示,与STI孵育48小时可抑制T细胞中IL-2R介导的蛋白质底物酪氨酸磷酸化,并且添加抗IFN-γ抗体和rIL-2并不能逆转这种抑制作用。这些结果表明,STI诱导的T细胞增殖抑制涉及T细胞中IL-2R功能和/或IL-2信号通路的缺陷。