Role of CD4 T cell help and costimulation in CD8 T cell responses during listeria monocytogenes infection
Role of CD4 T cell help and costimulation in CD8 T cell responses during listeria monocytogenes infection
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DOI：
10.4049/jimmunol.170.4.2053
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发表时间：
2003-02-15
影响因子：
4.4
通讯作者：
Shen, H
中科院分区：
文献类型：
--
作者：
Shedlock, DJ;Whitmire, JK;Shen, H
已知CD 4 T细胞通过经由CD 40-CD 40配体（L）相互作用激活APC来辅助CD 8 T细胞应答。然而，最近的数据表明，细菌产物可以通过Toll样受体直接激活APC，导致有效引发初始T细胞所必需的共刺激分子的上调。目前尚不清楚CD 4 T细胞辅助和各种共刺激途径在细菌感染期间CD 8 T细胞应答的发展中发挥什么作用。在这项研究中，我们研究了这些问题，使用细胞内的细菌，单核细胞增生李斯特菌，作为感染模型。在CD 4 T细胞耗竭、CD 4（-/-）和MHC II类-/-小鼠中，L.单核细胞增多症感染诱导CD 8 T细胞活化，并将表位特异性CD 8 T细胞致敏至与正常C57 BL/6小鼠中的水平相当的水平。此外，这些表位特异性CD 8 T细胞在CD 4（-/-）小鼠中建立了长期记忆，能够建立保护性回忆反应。体外分析表明，单核细胞增生李斯特菌直接刺激小鼠树突状细胞的激活和成熟。CD 8 T细胞对L.单核细胞增多症在CD 40 L（-/-）小鼠中是正常的，但在CD 28（-/-）和CD 137 L（-/-）小鼠中是缺陷的。这些数据表明，在感染原或免疫原可以直接激活APC的情况下，CD 8 T细胞应答较少依赖于通过CD 40-CD 40 L途径的CD 4 T细胞帮助，但涉及通过CD 137-CD 137 L和B7-CD 28相互作用的共刺激。
CD4 T cells are known to assist the CD8 T cell response by activating APC via CD40-CD40 ligand (L) interactions. However, recent data have shown that bacteria] products can directly activate APC through Toll-like receptors, resulting in up-regulation of costimulatory molecules necessary for the efficient priming of naive T cells. It remains unclear what role CD4 T cell help and various costimulation pathways play in the development of CD8 T cell responses during bacterial infection. In this study, we examined these questions using an intracellular bacterium, Listeria monocytogenes, as a model of infection. In CD4 T cell-depleted, CD4(-/-), and MHC class II-/- mice, L. monocytogenes infection induced CD8 T cell activation and primed epitope-specific CD8 T cells to levels commensurate with those in normal C57BL/6 mice. Furthermore, these epitope-specific CD8 T cells established long-term memory in CD4(-/-) mice that was capable of mounting a protective recall response. In vitro analysis showed that L monocytogenes directly stimulated the activation and maturation of murine dendritic cells. The CD8 T cell response to L. monocytogenes was normal in CD40L(-/-) mice but defective in CD28(-/-) and CD137L(-/-) mice. These data show that in situations where infectious agents or immunogens can directly activate APC, CD8 T cell responses are less dependent on CD4 T cell help via the CD40-CD40L pathway but involve costimulation through CD137-CD137L and B7-CD28 interactions.