Migration kinetics and final destination of type 1 and type 2 CD8 effector cells predict protection against pulmonary virus infection.
Migration kinetics and final destination of type 1 and type 2 CD8 effector cells predict protection against pulmonary virus infection.
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迁移动力学和1型和2型CD8效应细胞的最终目的地预测防止肺病毒感染的保护。
DOI：
10.1084/jem.189.2.423
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发表时间：
1999-01-18
期刊：
影响因子：
--
通讯作者：
Dutton RW
中科院分区：
文献类型：
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作者：
Cerwenka A;Morgan TM;Harmsen AG;Dutton RW
在过继性免疫疗法模型中，CD8 T 细胞提供针对局部病毒感染的保护的要求尚未明确定义。在这里，我们研究了来自克隆 4 T 细胞受体转基因小鼠的确定的体外生成的血凝素 (HA) 肽特异性初级 CD8 T 细胞效应器（分泌 1 型或 2 型细胞因子）对全流感病毒肺部感染的保护价值。产生 1 型和 2 型细胞因子（Tc1 和 Tc2）群体的细胞毒性 T 淋巴细胞具有相同的细胞毒性，但 Tc1 效应细胞而非 Tc2 效应细胞在感染早期降低了肺部病毒滴度。发现 Tc1 效应子介导的宿主恢复与干扰素 γ 的产生无关。与 Tc1 效应器相比，Tc2 效应器进入肺部的动力学延迟，进入肺部后，Tc2 效应器细胞不像 Tc1 效应器那样定位在受感染的气道上皮附近，而是在远离上皮的炎症细胞簇内发现。我们还表明，几种趋化因子受体的表达在 Tc1 和 Tc2 亚群中受到选择性调节。因此，CD8细胞群对抗肺流感病毒感染的保护价值与其在病毒感染部位发挥其效应潜力的能力密切相关。
The requirements for CD8 T cells to provide protection against a localized virus infection in models of adoptive immunotherapy are not well defined. Here we investigated the protective value of defined in vitro–generated hemagglutinin (HA) peptide-specific primary CD8 T cell effectors from the clone 4 T cell receptor transgenic mice, secreting type 1 or type 2 cytokines, against pulmonary infection with whole influenza virus. Cytotoxic T lymphocytes producing type 1 and type 2 cytokine (Tc1 and Tc2) populations were equally cytolytic, but Tc1 effectors and not Tc2 effectors reduced the pulmonary virus titer early during infection. Host recovery mediated by Tc1 effectors was found to be independent of interferon γ production. Tc2 effectors entered the lung with delayed kinetics as compared with Tc1 effectors, and after lung entry Tc2 effector cells did not localize near the infected airway epithelium as did Tc1 effectors but were found within clusters of inflammatory cells distant from the epithelium. We also show that the expression of several chemokine receptors was selectively regulated in the Tc1 and Tc2 subsets. Thus, the protective value of a CD8 cell population against pulmonary influenza virus infection is strongly correlated with its ability to exert its effector potential at the site of virus infection.