Jelley-Gibbs Dawn M, Dibble John P, Brown Deborah M, Strutt Tara M, McKinstry K Kai, Swain Susan L
Trudeau Institute, 154 Algonquin Avenue, Saranac Lake, NY 12983, USA.
J Immunol. 2007 Jun 15;178(12):7563-70. doi: 10.4049/jimmunol.178.12.7563.
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 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.
在慢性感染期间与抗原（Ag）相遇会导致抗原特异性CD8 T细胞产生表型和功能各异的亚群。流感是一种急性感染，也会导致产生类似的CD8 T细胞异质性，这可能归因于甲型流感病毒抗原的长期储存库，它们在病毒清除后仍能很好地刺激T细胞增殖。我们推测，流感特异性CD8 T细胞的异质性和T细胞记忆的维持需要新的CD8 T细胞招募到流感抗原的持续储存库中，就像流感特异性CD4 T细胞反应那样。然而，只有当幼稚CD8 T细胞在流感感染的第一周被激活时，才会发生强大的扩增以及产生高度分化的细胞溶解效应细胞和记忆T细胞。在感染第一周后激活新的幼稚CD8 T细胞，会导致产生数量少且功能不佳的效应细胞，几乎没有或没有细胞溶解活性，对记忆库的贡献可以忽略不计。因此，尽管在感染后期呈现流感抗原可能为维持肺中活化的CD8 T细胞群体提供一种机制，但很少有后来的CD8 T细胞被招募到功能性记忆T细胞库中。
