Cooper A M, Roberts A D, Rhoades E R, Callahan J E, Getzy D M, Orme I M
Department of Microbiology, Colorado State University, Fort Collins 80523, USA.
Immunology. 1995 Mar;84(3):423-32.
The early phase of acquired cellular immunity to Mycobacterium tuberculosis infection is mediated by the emergence of protective CD4 T lymphocytes that secrete cytokines including interferon-gamma (IFN-gamma), a molecule which is pivotal in the expression of resistance to tuberculosis. Recent evidence demonstrates that infection with M. tuberculosis induces peripheral blood mononuclear cells to release the cytokine interleukin-12 (IL-12), a molecule that promotes the emergence of T-helper type-1 (Th1), IFN-gamma-producing T cells. We demonstrate here that IL-12 mRNA expression was induced by M. tuberculosis infection both in vivo and in vitro and that exogenous administration of IL-12 to mice transiently resulted in increased resistance to the infection. IL-12 also increased the production of IFN-gamma by both splenocytes derived from infected animals treated in vivo and by antigen-stimulated CD4 cells from untreated infected animals, with maximal effects at times associated with the expansion of antigen-specific CD4 T cells in vivo. In the absence of a T-cell response, as seen in SCID mice or nude mice, IL-12 only slightly augmented the moderate bacteriostatic capacity of these immunocompromised mice. Neutralization of IL-12 by specific monoclonal antibodies resulted in a reduction in granuloma integrity and slowing of the capacity of the animal to control bacterial growth.
对结核分枝杆菌感染获得性细胞免疫的早期阶段，是由分泌包括γ干扰素（IFN-γ）在内的细胞因子的保护性CD4 T淋巴细胞的出现介导的，γ干扰素是一种在抗结核表达中起关键作用的分子。最近的证据表明，结核分枝杆菌感染可诱导外周血单核细胞释放细胞因子白细胞介素-12（IL-12），该分子可促进产生IFN-γ的1型辅助性T细胞（Th1）的出现。我们在此证明，结核分枝杆菌感染在体内和体外均可诱导IL-12 mRNA表达，并且向小鼠外源给予IL-12可短暂提高其对感染的抵抗力。IL-12还可增加体内经治疗的感染动物的脾细胞以及未经治疗的感染动物的抗原刺激的CD4细胞产生的IFN-γ，其最大效应与体内抗原特异性CD4 T细胞的扩增相关。在如SCID小鼠或裸鼠中所见的无T细胞应答的情况下，IL-12仅略微增强了这些免疫受损小鼠的中度抑菌能力。用特异性单克隆抗体中和IL-12会导致肉芽肿完整性降低以及动物控制细菌生长能力的减慢。
