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Trudeau Institute, Saranac Lake, NY 12983
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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Institutes of Health Grants HL63925, P01AI45666, and P01AI45530, Northeast Biodefense Center U54-AI057158-Lipkin, and by the Trudeau Institute.
2 Address correspondence and reprint requests to Dr. Dawn M. Jelley-Gibbs, 154 Algonquin Avenue, Saranac Lake, NY 12983. E-mail address: djgibbs{at}trudeauinstitute.org
3 Abbreviations used in this paper: Tg, transgenic; HA Tg, hemagglutinin protein Tg; MDCK, Madin-Darby canine kidney; PA, polymerase; DLN, draining lymph node; WT, sham thymectomy; i.n., intranasal; GrB, granzyme B.
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