Persistent depots of influenza antigen fail to induce a cytotoxic CD8 T cell response

DM Jelley-Gibbs, JP Dibble, DM Brown… - The Journal of …, 2007 - journals.aai.org
DM Jelley-Gibbs, JP Dibble, DM Brown, TM Strutt, KK McKinstry, SL Swain
The Journal of Immunology, 2007journals.aai.org
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 …
Abstract
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.
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