A critical role for CD40-CD40 ligand interactions in amplification of the mucosal CD8 T cell response.
A critical role for CD40-CD40 ligand interactions in amplification of the mucosal CD8 T cell response.
复制标题
CD40-CD40配体相互作用在粘膜CD8 T细胞反应扩增中的关键作用。
DOI：
10.1084/jem.190.9.1275
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发表时间：
1999-11-01
影响因子：
15.3
通讯作者：
Masopust, D
中科院分区：
文献类型：
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作者：
Lefrancois, L;Olson, S;Masopust, D
通过体内过继转移T细胞受体转基因T细胞和主要组织相容性复合体(MHC)I类四聚体追踪抗原特异性T细胞，评价CD40配体(CD40L)在CD8 T细胞活化中的作用。可溶性抗原免疫可诱导CD8细胞进入肠粘膜和细胞毒性T淋巴细胞(CTL)分化，而次级淋巴组织中的CD8细胞增殖但不具细胞溶解功能。同时阻断CD40L或不阻断CD40的免疫实验表明，CD8T细胞在粘膜中的聚集依赖于CD40L。此外，CD40L的激活是通过CD8细胞表达的CD40L介导的，因为在过继转移到CD40L缺陷小鼠后，抗CD40L的单抗会产生抑制作用。然而，正常小鼠和−/−小鼠粘膜中的CD8T细胞具有相同的杀伤活性，提示CD40L不是CTL分化所必需的。CD8细胞的出现在很大程度上依赖于CD40-CD40L的相互作用。CD8T细胞的粘膜CTL反应不依赖于MHC-II类和IL-12。这一结果建立了CD40L介导的CD8 T细胞直接激活的新途径。
The role of CD40 ligand (CD40L) in CD8 T cell activation was assessed by tracking antigen-specific T cells in vivo using both adoptive transfer of T cell receptor transgenic T cells and major histocompatibility complex (MHC) class I tetramers. Soluble antigen immunization induced entry of CD8 cells into the intestinal mucosa and cytotoxic T lymphocyte (CTL) differentiation, whereas CD8 cells in secondary lymphoid tissue proliferated but were not cytolytic. Immunization concurrent with CD40L blockade or in the absence of CD40 demonstrated that accumulation of CD8 T cells in the mucosa was CD40L dependent. Furthermore, activation was mediated through CD40L expressed by the CD8 cells, since inhibition by anti-CD40L monoclonal antibodies occurred after adoptive transfer to CD40L-deficient mice. However, mucosal CD8 T cells in normal and CD40−/− mice were equivalent killers, indicating that CD40L was not required for CTL differentiation. Appearance of virus-specific mucosal, but not splenic, CD8 cells also relied heavily on CD40–CD40L interactions. The mucosal CTL response of transferred CD8 T cells was MHC class II and interleukin 12 independent. The results established a novel pathway of direct CD40L-mediated CD8 T cell activation.