Flynn J L, Goldstein M M, Triebold K J, Koller B, Bloom B R
Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, NY 10461.
Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):12013-7. doi: 10.1073/pnas.89.24.12013.
Mice with a targeted disruption in the beta 2-microglobulin (beta 2m) gene, which lack major histocompatibility complex class I molecules and consequently fail to develop functional CD8 T cells, provided a useful model for assessing the role of class I-restricted T cells in resistance to infection with virulent Mycobacterium tuberculosis. Of mutant beta 2m-/-mice infected with virulent 10(6) M. tuberculosis, 70% were dead or moribund after 6 weeks, while all control mice expressing the beta 2m gene remained alive for > 20 weeks. Granuloma formation occurred in mutant and control mice, but far greater numbers of tubercle bacilli were present in the lungs of mutant mice than in controls, and caseating necrosis was seen only in beta 2m-/-lungs. In contrast, no differences were seen in the course of infection of mutant and control mice with an avirulent vaccine strain, bacille Calmette-Guérin (BCG). Immunization with BCG vaccine prolonged survival of beta 2m-/-mice after challenge with M. tuberculosis for 4 weeks but did not protect them from death. These data indicate that functional CD8 T cells, and possibly T cells bearing gamma delta antigen receptor, are a necessary component of a protective immune response to M. tuberculosis in mice.
β2-微球蛋白（β2m）基因发生靶向破坏的小鼠缺乏主要组织相容性复合体I类分子，因此无法发育出功能性CD8 T细胞，这为评估I类限制性T细胞在抵抗强毒结核分枝杆菌感染中的作用提供了一个有用的模型。在感染了10^6个强毒结核分枝杆菌的突变型β2m-/-小鼠中，70%在6周后死亡或濒死，而所有表达β2m基因的对照小鼠存活超过20周。突变型和对照小鼠中均形成了肉芽肿，但突变型小鼠肺中的结核杆菌数量远多于对照小鼠，并且仅在β2m-/-小鼠的肺中出现了干酪样坏死。相比之下，突变型和对照小鼠感染无毒疫苗株卡介苗（BCG）的感染过程没有差异。用BCG疫苗免疫可使β2m-/-小鼠在感染结核分枝杆菌后存活时间延长4周，但不能保护它们免于死亡。这些数据表明，功能性CD8 T细胞以及可能带有γδ抗原受体的T细胞是小鼠对结核分枝杆菌保护性免疫反应的必要组成部分。
