Persistent depots of influenza antigen fail to induce a cytotoxic CD8 T cell response
Persistent depots of influenza antigen fail to induce a cytotoxic CD8 T cell response
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DOI：
10.4049/jimmunol.178.12.7563
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发表时间：
2007-06-15
影响因子：
4.4
通讯作者：
Swain, Susan L.
中科院分区：
文献类型：
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作者：
Jelley-Gibbs, Dawn M.;Dibble, John P.;Swain, Susan L.
在慢性感染期间遇到Ag会导致Ag特异性CD8 T细胞的表型和功能异质亚群的产生。流感是一种急性感染，可导致相似的CD8 T细胞异质性的产生，这可能是由于在病毒清除后，长时间存在的流感Ags能够刺激T细胞增殖。我们假设流感特异性CD8 T细胞的异质性和T细胞记忆的维持需要招募新的CD8 T细胞到持续的流感银库，就像流感特异性CD4 T细胞反应的情况一样。然而，只有在流感感染的前14周内启动初始CD8 T细胞时，才会出现高度分化的细胞溶解效应细胞和记忆T细胞的强劲扩增和产生。在感染第一周后启动新的初始CD8 T细胞导致少量功能差的效应细胞，几乎没有细胞溶解活性，对记忆池的贡献可以忽略不计。因此，尽管流感抗原在感染后期的呈现可能为维持肺中CD8 T细胞的激活群提供了一种机制，但很少有迟发CD8 T细胞被招募到功能记忆T细胞库中。
Encounter with Ag during chronic infections results in the generation of phenotypically and functionally heterogeneous subsets of Ag-specific CD8 T cells. Influenza, an acute infection, results in the generation of similar CD8 T cell heterogeneity, which may be attributed to long-lived depots of flu Ags that stimulate T cell proliferation well after virus clearance. We hypothesized that the heterogeneity of flu-specific CD8 T cells and maintenance of T cell memory required the recruitment of new CD8 T cells to persistent depots of flu Ag, as was the case for flu-specific CD4 T cell responses. However, robust expansion and generation of highly differentiated cytolytic effectors and memory T cells only occurred when naive CD8 T cells were primed during the first 14 week of flu infection. Priming of new naive CD8 T cells after the first week of infection resulted in low numbers of poorly functional effectors, with little to no cytolytic activity, and a negligible contribution to the memory pool. Therefore, although the presentation of flu Ag during the late stages of infection may provide a mechanism for maintaining an activated population of CD8 T cells in the lung, few latecomer CD8 T cells are recruited into the functional memory T cell pool.