Cooper A M, Dalton D K, Stewart T A, Griffin J P, Russell D G, Orme I M
Department of Microbiology, Colorado State University, Fort Collins 80523.
J Exp Med. 1993 Dec 1;178(6):2243-7. doi: 10.1084/jem.178.6.2243.
The expression of protective immunity to Mycobacterium tuberculosis in mice is mediated by T lymphocytes that secrete cytokines. These molecules then mediate a variety of roles, including the activation of parasitized host macrophages, and the recruitment of other mononuclear phagocytes to the site of the infection in order to initiate granuloma formation. Among these cytokines, interferon gamma (IFN-gamma) is believed to play a key role is these events. In confirmation of this hypothesis, we show in this study that mice in which the IFN-gamma gene has been disrupted were unable to contain or control a normally sublethal dose of M. tuberculosis, delivered either intravenously or aerogenically. In such mice, a progressive and widespread tissue destruction and necrosis, associated with very high numbers of acid-fast bacilli, was observed. In contrast, despite the lack of protective immunity, some DTH-like reactivity could still be elicited. These data, therefore, indicate that although IFN-gamma may not be needed for DTH expression, it plays a pivotal and essential role in protective cellular immunity to tuberculosis infection.
小鼠对结核分枝杆菌保护性免疫的表达是由分泌细胞因子的T淋巴细胞介导的。这些分子随后介导多种作用,包括激活被寄生的宿主巨噬细胞,以及将其他单核吞噬细胞募集到感染部位以启动肉芽肿形成。在这些细胞因子中,γ干扰素(IFN-γ)被认为在这些事件中起关键作用。为证实这一假设,我们在本研究中表明,IFN-γ基因被破坏的小鼠无法控制或抵御正常情况下亚致死剂量的经静脉或空气传播的结核分枝杆菌。在这类小鼠中,观察到与大量抗酸杆菌相关的进行性广泛组织破坏和坏死。相比之下,尽管缺乏保护性免疫,但仍可引发一些类似迟发型超敏反应(DTH)的反应。因此,这些数据表明,虽然IFN-γ可能不是DTH表达所必需的,但它在针对结核感染的保护性细胞免疫中起关键和重要作用。