Continuous recruitment of naive T cells contributes to heterogeneity of antiviral CD8 T cells during persistent infection

Vaiva Vezys, David Masopust, Christopher C. Kemball, Daniel L. Barber, Leigh A. O'Mara, Christian P. Larsen, Thomas C. Pearson, Rafi Ahmed, Aron E. Lukacher

Research output: Contribution to journalArticle

159 Scopus citations

Abstract

Numerous microbes establish persistent infections, accompanied by antigen-specific CD8 T cell activation. Pathogen-specific T cells in chronically infected hosts are often phenotypically and functionally variable, as well as distinct from T cells responding to nonpersistent infections; this phenotypic heterogeneity has been attributed to an ongoing reencounter with antigen. Paradoxically, maintenance of memory CD8 T cells to acutely resolved infections is antigen independent, whereas there is a dependence on antigen for T cell survival in chronically infected hosts. Using two chronic viral infections, we demonstrate that new naive antigen-specific CD8 T cells are primed after the acute phase of infection. These newly recruited T cells are phenotypically distinct from those primed earlier. Long-lived antiviral CD8 T cells are defective in self-renewal, and lack of thymic output results in the decline of virus-specific CD8 T cells, indicating that newly generated T cells preserve antiviral CD8 T cell populations during chronic infection. These findings reveal a novel role for antigen in maintaining virus-specific CD8 T cells during persistent infection and provide insight toward understanding T cell differentiation in chronic infection. JEM

Original languageEnglish (US)
Pages (from-to)2263-2269
Number of pages7
JournalJournal of Experimental Medicine
Volume203
Issue number10
DOIs
StatePublished - 2006

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