TY - JOUR
T1 - Persistent depots of influenza antigen fail to induce a cytotoxic CD8 T cell response
AU - Jelley-Gibbs, Dawn M.
AU - Dibble, John P.
AU - Brown, Deborah M.
AU - Strutt, Tara M.
AU - McKinstry, K. Kai
AU - Swain, Susan L.
PY - 2007/6/15
Y1 - 2007/6/15
N2 - 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.
AB - 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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U2 - 10.4049/jimmunol.178.12.7563
DO - 10.4049/jimmunol.178.12.7563
M3 - Article
C2 - 17548591
AN - SCOPUS:34250186360
SN - 0022-1767
VL - 178
SP - 7563
EP - 7570
JO - Journal of Immunology
JF - Journal of Immunology
IS - 12
ER -