Abstract
Viral infections often induce robust T cell responses that are long-lived and protective. However, it is unclear to what degree systemic versus mucosal infection influences the generation of effector and memory T cells. In this study, we characterized memory CD8+ T cells generated after respiratory influenza virus infection and compared the phenotypic and functional qualities of these cells with memory T cells generated after systemic infection with lymphocytic choriomeningitis virus (LCMV). Using a recombinant influenza virus expressing the LCMV gp33–41 epitope and TCR transgenic CD8+ T cells with a fixed TCR, we compared responses to the same Ag delivered by mucosal or systemic viral infection. Memory cells generated postinfection with either virus showed only a few phenotypic differences. Yet, influenza memory T cells produced lower amounts of effector cytokines upon restimulation and displayed reduced proliferation compared with LCMV-induced memory cells. Strikingly, we observed reduced expansion of spleen- and, in particular, lung-derived influenza memory cells after recall in vivo, which correlated with reduced early protection from secondary infection. These findings suggest that qualitatively different memory CD8+ T cells are generated after respiratory or systemic virus infections.
Footnotes
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This work was supported, in part, by National Institutes of Health Grants U01 AI070469 (to A.G.-S.) and U54 AI057157-05 (to R.A.). S.N.M. was supported by a C.J. Martin fellowship from the National Health and Medical Research Council of Australia.
- Received April 12, 2010.
- Accepted June 7, 2010.