Immunosuppressive roles for IL-10 and IL-4 in human infection. In vitro modulation of T cell responses in leprosy.
Immunosuppressive roles for IL-10 and IL-4 in human infection. In vitro modulation of T cell responses in leprosy.
复制标题
DOI：
10.4049/jimmunol.150.12.5501
复制
发表时间：
1993-06
影响因子：
4.4
通讯作者：
P. Sieling;J. Abrams;M. Yamamura;Padmini Salgame;Barry R. Bloom;T. Rea;R. Modlin
中科院分区：
文献类型：
--
作者：
P. Sieling;J. Abrams;M. Yamamura;Padmini Salgame;Barry R. Bloom;T. Rea;R. Modlin
IL-10和IL-4已被证明对细胞介导的免疫反应具有抑制作用。我们之前对麻风病的研究表明，IL-10和IL-4 mRNA在麻风病患者的病变中优先表达，这些患者表现为广泛感染的免疫无反应个体。为了更精确地定义这两种细胞因子在感染免疫应答中的调节作用，我们研究了体外对麻风分枝杆菌的反应。麻风分枝杆菌可触发患者和健康供体PBMC释放IL-10；IL-10的主要来源是单核细胞/巨噬细胞。中和性抗IL-10单抗对PBMC的刺激表明，内源性IL-10的产生抑制了PBMC的增殖和tnf - α、GM-CSF和ifn - γ的释放。矛盾的是，使用中和抗IL-4单抗的研究表明，内源性IL-4的产生在麻风患者中最显著地增强了PBMC的增殖反应。我们发现il -4在体外扩增了麻风患者的CD8+ T细胞。来自麻风病患者的CD8+ T细胞已被证明抑制CD4+ T细胞反应，部分原因是IL-4的释放。我们的研究表明，内源性IL-4的产生抑制了IL-10的分泌，同时增加了tnf - α和GM-CSF的释放。目前的数据表明，总的来说，IL-4和IL-10有助于人类传染病的免疫抑制。
IL-10 and IL-4 have been shown to exert an inhibitory effect on cell-mediated immune responses. Our previous studies of leprosy demonstrated that IL-10 and IL-4 mRNA were preferentially expressed in lesions from lepromatous patients, those immunologically unresponsive individuals that manifest widespread infection. To define more precisely the regulatory roles of these two cytokines in the immune response to infection, we studied in vitro responses to Mycobacterium leprae. M. leprae triggered IL-10 release from PBMC of patients and healthy donors; the predominant source of the IL-10 was found to be monocytes/macrophages. Stimulation of PBMC in the presence of neutralizing anti-IL-10 mAb indicated that endogenous IL-10 production inhibits PBMC proliferation and release of TNF-alpha, GM-CSF, and IFN-gamma. Paradoxically, studies using neutralizing anti-IL-4 mAb indicated that endogenous IL-4 production enhances PBMC proliferative responses most strikingly in lepromatous patients. We found that rIL-4 expanded CD8+ T cells from lepromatous patients in vitro. CD8+ T cells from lepromatous patients have been shown to suppress CD4+ T cell responses, in part by the release of IL-4. Our study indicated that endogenous IL-4 production inhibited IL-10 secretion and, concomitantly, increased TNF-alpha and GM-CSF release. The present data suggest that, on balance, IL-4 and IL-10 contribute to immunosuppression in human infectious disease.