Ohtsuka K, Sato K, Watanabe H, Kimura M, Asakura H, Abo T
Department of Immunology, Niigata University School of Medicine, Japan.
Cell Immunol. 1995 Mar;161(1):112-24. doi: 10.1006/cimm.1995.1015.
We investigated how NK cells, extrathymic T cells, and thymus-derived T cells are activated in mice during infection with an intracellular pathogen, Listeria (L.) monocytogenes. Although macrophages and granulocytes are known to be involved in the elimination of this pathogen in an early phase of infection, it was still controversial what type of lymphocytes are induced as effectors in subsequent phases. When mice were ip injected with 1 x 10(3) L. monocytogenes (a sublethal dose), a prominent increase in the number of mononuclear cells in the liver and spleen was induced. Phenotypic analysis revealed that serial induction of lymphocyte subsets, NK cells-->extrathymic T cells-->thymus-derived T cells, occurred in these organs. Extrathymic T cells were estimated to have intermediate CD3 and a high level of IL-2 receptor beta-chain on the surface (i.e., intermediate CD3 cells). These mice became free from infection after 2 weeks. In the case of oral administration, 1 x 10(3) L. monocytogenes increased the number of cells in the liver and the number of intraepithelial and lamina propria lymphocytes in the intestine. Phenotypic analysis also showed a sequential induction of lymphocyte subsets in the liver and the induction of extrathymic T cells in the intestine. Preelimination of intermediate TCR cells and NK cells by in vivo treatment with anti-LFA-1 mAb made mice susceptible to an ip injected sublethal dose of L. monocytogenes. These results reveal a unique order of lymphocyte induction during listerial infection and indicate that extrathymic T cells might be one of the important cells in achieving resistance against L. monocytogenes.
我们研究了在小鼠感染细胞内病原体单核细胞增生李斯特菌(Listeria [L.] monocytogenes)期间,自然杀伤细胞(NK细胞)、胸腺外T细胞和胸腺来源的T细胞是如何被激活的。虽然已知巨噬细胞和粒细胞在感染早期参与清除这种病原体,但在后续阶段诱导何种类型的淋巴细胞作为效应细胞仍存在争议。当给小鼠腹腔注射1×10³个单核细胞增生李斯特菌(亚致死剂量)时,肝脏和脾脏中的单核细胞数量显著增加。表型分析显示,在这些器官中淋巴细胞亚群呈系列诱导,即NK细胞→胸腺外T细胞→胸腺来源的T细胞。胸腺外T细胞估计表面具有中等水平的CD3和高水平的白细胞介素-2受体β链(即中等CD3细胞)。这些小鼠在2周后摆脱感染。在口服给药的情况下,1×10³个单核细胞增生李斯特菌增加了肝脏中的细胞数量以及肠道上皮内和固有层淋巴细胞的数量。表型分析还显示肝脏中淋巴细胞亚群的顺序诱导以及肠道中胸腺外T细胞的诱导。通过体内用抗LFA-1单克隆抗体处理预先清除中等TCR细胞和NK细胞,使小鼠对腹腔注射的亚致死剂量的单核细胞增生李斯特菌易感。这些结果揭示了李斯特菌感染期间淋巴细胞诱导的独特顺序,并表明胸腺外T细胞可能是实现对单核细胞增生李斯特菌抗性的重要细胞之一。