IL-12 regulates T helper type 1 cytokine responses in human infectious disease.
IL-12 regulates T helper type 1 cytokine responses in human infectious disease.
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DOI：
10.4049/jimmunol.153.8.3639
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发表时间：
1994-10
影响因子：
4.4
通讯作者：
PA Sieling;X. Wang;MK Gately;JL Oliveros;T. McHugh;PF Barnes;Sf Wolf;L. Golkar;M. Yamamura;Y. Yogi;K. Uyemura;TH Rea;RL Modlin
中科院分区：
文献类型：
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作者：
PA Sieling;X. Wang;MK Gately;JL Oliveros;T. McHugh;PF Barnes;Sf Wolf;L. Golkar;M. Yamamura;Y. Yogi;K. Uyemura;TH Rea;RL Modlin
我们以麻风病谱系为模型，研究了 IL-12 在调节人类传染病中 T 细胞和细胞因子反应中的作用。结核病患者对麻风分枝杆菌产生强烈的 T 细胞反应，在病变部位产生 1 型细胞因子 IL-2 和 IFN-γ；而麻风病患者表现出对麻风分枝杆菌的弱 T 细胞反应，并在病变中产生 2 型细胞因子 IL-4 和 IL-10。我们发现，通过 PCR 扩增测量的 IL-12 p40 mRNA 和通过免疫组织化学测量的 IL-12 p70 mRNA 的表达，在结核样病变中比在麻风病病变中高 10 倍。 rIL-4 和 rIL-10 抑制麻风分枝杆菌刺激单核细胞释放 IL-12 的能力。向IL-12添加中和抗体可阻断结核分枝杆菌诱导的T细胞增殖。此外，rIL-12 刺激来自结核样病变的 CD4+ 1 型 T 细胞克隆的增殖，但不刺激来自麻风病灶的 CD8+ 2 型 T 细胞克隆的增殖。然而，两者均对 rIL-2、rIL-12 产生反应，增强了麻风病患者中麻风分枝杆菌特异性 T 细胞增殖，从而导致 CD4+ T 细胞选择性扩增并增加 T 细胞 IFN-γ 的产生。这些数据表明，IL-12 是人类传染病中 1 型细胞因子反应产生的重要介质。
We investigated the role of IL-12 in regulating T cell and cytokine responses in human infectious disease by using the spectrum of leprosy as a model. Tuberculoid patients mount strong T cell responses to Mycobacterium leprae, with production of the type 1 cytokines IL-2 and IFN-gamma in lesions; whereas lepromatous patients manifest weak T cell responses to M. leprae, with production of the type 2 cytokines IL-4 and IL-10 in lesions. We found expression of IL-12 p40 mRNA, as measured by PCR amplification, and IL-12 p70, as measured by immunohistochemistry, to be 10-fold greater in tuberculoid lesions than in lepromatous lesions. The ability of M. leprae to stimulate release of IL-12 from monocytes was inhibited by rIL-4 and rIL-10. M. leprae-induced T cell proliferation in tuberculoid patients was blocked by the addition of neutralizing Abs to IL-12. Furthermore, rIL-12 stimulated proliferation of CD4+ type 1 T cell clones from tuberculoid lesions, but not CD8+ type 2 T cell clones from lepromatous lesions; however, both responded to rIL-2, rIL-12 augmented M. leprae-specific T cell proliferation in lepromatous patients, thereby causing the selective expansion of CD4+ T cells and increasing T cell IFN-gamma production. These data indicate that IL-12 is an important mediator in the generation of the type 1 cytokine response in human infectious disease.