Gamma interferon-producing CD4+ T lymphocytes in the lung correlate with resistance to infection with Mycobacterium tuberculosis
Gamma interferon-producing CD4+ T lymphocytes in the lung correlate with resistance to infection with Mycobacterium tuberculosis
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DOI：
10.1128/iai.69.4.2666-2674.2001
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发表时间：
2001-04-01
影响因子：
3.1
通讯作者：
Behar, SM
中科院分区：
文献类型：
--
作者：
Chackerian, AA;Perera, TV;Behar, SM
人类免疫系统有效地限制了结核分枝杆菌在大多数感染个体中的复制。只有5%到10%的感染者会发展为临床结核病，这是免疫系统无法控制感染的一个迹象。我们研究了C3 H/HeJ（C3 H）和C57 BL/6（B6）近交系小鼠品系，这两种品系对结核病的易感性不同，以确定成功的抗结核分枝杆菌免疫应答的免疫决定因素。结核病和建立一个系统，以确定影响结核病易感性的基因。我们发现耐药B6小鼠能够控制肺和脾的感染，而易感C3 H小鼠不能限制细菌生长，特别是在肺中，并在4周内死于感染。我们确定，C3 H小鼠的易感性是独立的Toll样受体4（tlr 4）的遗传位点和等位基因的主要组织相容性复合体的差异。虽然两种小鼠品系的脾脏免疫应答相似，但感染小鼠肺部的局部免疫应答差异很大。耐药B6小鼠的肺免疫应答的特征在于产生γ干扰素（IFN-γ）的CD 4（+）和CD 8（+）淋巴细胞的早期流入。相反，C3 H小鼠肺中的免疫应答的特征在于产生很少IFN-γ的淋巴细胞的延迟和减少的流入。这些结果表明，肺中产生IFN-γ的淋巴细胞的早期出现在抵抗M.结核
The human immune system efficiently limits the replication of Mycobacterium tuberculosis in most infected individuals. Only 5 to 10% of infected people develop clinical tuberculosis, a sign of the inability of the immune system to control the infection. We have studied the C3H/HeJ (C3H) and C57BL/6 (B6) inbred mouse strains, which differ in their susceptibility to tuberculosis, in order to ascertain the immunological determinants of a successful immune response against M. tuberculosis and to establish a system to identify genes that influence susceptibility to tuberculosis. We found that the resistant B6 mice were able to control infection in both the lung and spleen, while susceptible C3H mice were incapable of limiting bacteria growth, especially in the lung, and succumbed to infection within 4 weeks. We determined that the susceptibility of C3H mice was independent of the Toll-like receptor 4 (tlr4) genetic locus and allelic major histocompatibility complex differences. Although the splenic immune responses were similar in the two mouse strains, the local immune responses in the lungs of the infected mice differed greatly. The pulmonary immune response in resistant B6 mice was characterized by an early influx of both CD4(+) and CD8(+) lymphocytes that produced gamma interferon (IFN-gamma), In contrast, the immune response of C3H mice in the lung was characterized by a delayed and decreased influx of lymphocytes, which produced little IFN-gamma. These results suggest an important role for the early appearance of IFN-gamma -producing lymphocytes in the lung in resistance to infection with M. tuberculosis.