Journal
JOURNAL OF IMMUNOLOGY
Volume 178, Issue 12, Pages 7563-7570Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.178.12.7563
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Funding
- NHLBI NIH HHS [HL 63925] Funding Source: Medline
- NIAID NIH HHS [P01 AI 45666, P01 AI 45530, U54 AI 057158] Funding Source: Medline
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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.
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