Flynn J L, Goldstein M M, Chan J, Triebold K J, Pfeffer K, Lowenstein C J, Schreiber R, Mak T W, Bloom B R
Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pennsylvania 15261, USA.
Immunity. 1995 Jun;2(6):561-72. doi: 10.1016/1074-7613(95)90001-2.
Understanding the immunological mechanisms of protection and pathogenesis in tuberculosis remains problematic. We have examined the extent to which tumor necrosis factor-alpha (TNF alpha) contributes to this disease using murine models in which the action of TNF alpha is inhibited. TNF alpha was neutralized in vivo by monoclonal antibody; in addition, a mouse strain with a disruption in the gene for the 55 kDa TNF receptor was used. The data from both models established that TNF alpha and the 55 kDa TNF receptor are essential for protection against tuberculosis in mice, and for reactive nitrogen production by macrophages early in infection. Granulomas were formed in equal numbers in control and experimental mice, but necrosis was observed only in mice deficient in TNF alpha or TNF receptor. TNF alpha and the 55 kDa TNF receptor are necessary conditions for protection against murine M. tuberculosis infection, but are not solely responsible for the tissue damage observed.
了解结核病中保护和发病机制的免疫机制仍然存在问题。我们使用肿瘤坏死因子-α（TNFα）作用受到抑制的小鼠模型，研究了TNFα在这种疾病中的作用程度。通过单克隆抗体在体内中和TNFα；此外，还使用了一种55 kDa TNF受体基因发生破坏的小鼠品系。来自这两种模型的数据表明，TNFα和55 kDa TNF受体对于小鼠抵抗结核病以及感染早期巨噬细胞产生反应性氮至关重要。对照小鼠和实验小鼠中形成的肉芽肿数量相等，但仅在TNFα或TNF受体缺陷的小鼠中观察到坏死。TNFα和55 kDa TNF受体是抵抗小鼠结核分枝杆菌感染的必要条件，但并非是观察到的组织损伤的唯一原因。
