The relative importance of T cell subsets in immunity and immunopathology of airborne Mycobacterium tuberculosis infection in mice.
The relative importance of T cell subsets in immunity and immunopathology of airborne Mycobacterium tuberculosis infection in mice.
复制标题
T细胞亚群在小鼠中的肺结核感染的免疫和免疫病理学中的相对重要性。
DOI：
10.1084/jem.193.3.271
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发表时间：
2001-02-05
影响因子：
15.3
通讯作者：
North, R J
中科院分区：
文献类型：
--
作者：
Mogues, T;Goodrich, M E;Ryan, L;LaCourse, R;North, R J
将不能产生αβ T细胞、γδ T细胞、I类主要组织相容性复合体（MHC）、II类MHC、干扰素（IFN）-γ或诱导型一氧化氮合酶（NOS 2）的野生型（WT）和靶向突变小鼠通过气溶胶用结核分枝杆菌（Mt B）感染，并随时间监测它们（a）控制感染，（B）在感染部位发生组织病理学，（C）生存。WT小鼠从第20天起获得了控制感染并将其保持在稳定水平的能力，这与感染部位巨噬细胞主导的肺泡炎的发展、IFN-γ和NOS 2 mRNA的合成增加以及中位生存时间（MST）为258.5 d有关。在不存在αβ T细胞的情况下，Mtb进行性快速生长，诱导坏死的嗜中性粒细胞占主导地位的肺病理学，杀死MST为48 d的小鼠。在不存在CD 4介导的免疫力的情况下（II类−/−小鼠），肺部和其他器官中的进行性细菌生长持续超过20天，导致MST为77天。相比之下，在不存在CD 8 T细胞介导的免疫的情况下，肺部感染被控制在高1个对数的稳定水平，诱导与WT小鼠相似的组织病理学应答，并导致MST为232天。
Wild-type (WT) and targeted-mutant mice incapable of making αβ T cells, γδ T cells, class I major histocompatibility complex (MHC), class II MHC, interferon (IFN)-γ, or inducible nitric oxide synthase (NOS2), were infected with Mycobacterium tuberculosis (Mtb) by aerosol, and monitored over time for their ability to (a) control infection, (b) develop histopathology at sites of infection, and (c) survive. WT mice acquired the ability to control and to hold infection at a stationary level from day 20 on. This was associated with the development of a macrophage-dominated alveolitis at sites of infection, with increased synthesis of IFN-γ and NOS2 mRNA, and with an median survival time (MST) of 258.5 d. In the absence of αβ T cells, Mtb grew progressively and rapidly to induce a necrotic, neutrophil-dominated lung pathology that killed mice with an MST of 48 d. In the absence of CD4-mediated immunity (class II−/− mice), progressive bacterial growth continued in the lungs and in other organs beyond day 20, resulting in an MST of 77 d. By contrast, in the absence of CD8 T cell–mediated immunity, lung infection was controlled at a 1 log higher stationary level that induced a similar histopathologic response to that of WT mice, and resulted in an MST of 232 d.