Yoneda T
Second Department of Internal Medicine, Nara Medical University, Japan.
Kekkaku. 1996 Nov;71(11):625-31.
Although natural killer (NK) cells, which lyse certain tumors in vitro, have been shown to provide early defense mechanism against cancer growth and viral infection, possible role in the host defense against pulmonary tuberculosis remains undefined. A series of my studies have recently provided several evidence supporting the involvement of NK cells in the immunopathology of pulmonary tuberculosis. NK cell activity in patients with active pulmonary tuberculosis was significantly augmented compared with that in age-, sex- matched healthy controls, which suggests NK cells are activated in vivo in pulmonary tuberculosis. Lung NK cells from BCG-infected mice also are shown to be activated. Asialo GM 1 was demonstrated to be a novel surface marker of mice NK cells, which inhibited activation of NK cells by interferon. Chronic intractable tuberculosis was classified with a combination of NK cell activity and delayed-type hypersensitivity reaction to 2, 4-dinitrochrolbenzene. Subgroup defined with high NK cell activity and normal delayed-type hypersensitivity was characterized with moderate radiographical lesions and stable clinical course, suggesting the immune-spectrum classification was associated with clinical manifestations. Malnutrition has been suggested to be a risk factor associated with the development and reactivation of pulmonary tuberculosis. NK cell activity was significantly correlated with visceral proteins. IL-2 producing capability was significantly decreased in patients with serum albumin less than 3.5 g/dl. More recently, I established an in vitro system evaluating quantitative capability for intracellular killing by human monocytes, in which monocyte phagocytize Mycobacterium tuberculosis and subsequently inhibit intracellular replication of the organisms by adding some cytokines or cells. Purified NK cells by using discontinuous gradient centrifugation and magnetic separation technique were added to M. tuberculosis-infected monocytes monolayer. Purified NK cells inhibit intracellular replication within monocytes in dose response manner.
虽然自然杀伤（NK）细胞在体外可裂解某些肿瘤，已被证明能为抵抗癌症生长和病毒感染提供早期防御机制，但其在宿主抵御肺结核中的可能作用仍不明确。我最近的一系列研究提供了若干证据，支持NK细胞参与肺结核的免疫病理学过程。与年龄、性别匹配的健康对照相比，活动性肺结核患者的NK细胞活性显著增强，这表明NK细胞在肺结核患者体内被激活。卡介苗感染小鼠的肺NK细胞也显示被激活。去唾液酸GM1被证明是小鼠NK细胞的一种新型表面标志物，它可抑制干扰素对NK细胞的激活。慢性难治性肺结核根据NK细胞活性和对2,4 -二硝基氯苯的迟发型超敏反应进行分类。NK细胞活性高且迟发型超敏反应正常的亚组，其影像学病变中等且临床病程稳定，这表明免疫谱分类与临床表现相关。营养不良被认为是与肺结核发生和复发相关的一个危险因素。NK细胞活性与内脏蛋白显著相关。血清白蛋白低于3.5 g/dl的患者，其产生白细胞介素 - 2的能力显著降低。最近，我建立了一个体外系统来评估人单核细胞的细胞内杀伤定量能力，在该系统中，单核细胞吞噬结核分枝杆菌，随后通过添加一些细胞因子或细胞来抑制该菌的细胞内复制。通过不连续梯度离心和磁性分离技术纯化的NK细胞被添加到感染结核分枝杆菌的单核细胞单层中。纯化的NK细胞以剂量反应方式抑制单核细胞内的复制。
