Chronic Antigen Stimulation Alone Is Sufficient to Drive CD8(+) T Cell Exhaustion

Christine M. Bucks, Jillian A. Norton, Alina C. Boesteanu, Yvonne M. Mueller, Peter D. Katsikis*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

121 Citations (Scopus)
20 Downloads (Pure)

Abstract

The failure of CD8(+) T cells to respond to chronic infection has been termed "exhaustion" and describes the condition in which CD8(+) T cells exhibit reduced differentiation, proliferation, and effector function. CD8(+) T cell exhaustion has been extensively studied in the murine model of chronic infection, lymphocytic choriomeningitis virus (LCMV). Although LCMV-based studies have yielded many interesting findings, they have not allowed for discrimination between the roles of cytokine- and Ag-driven exhaustion. We have created a system of chronic Ag stimulation using murine influenza A virus that leads to exhaustion and functional disability of virus-specific CD8(+) T cells, in the absence of high viral titers, sustained proinflammatory cytokine production and lymphocyte infection. Our findings show that Ag alone is sufficient to drive CD8(+) T cell impairment, that Ag-driven loss of virus-specific CD8(+) T cells is TRAIL mediated, and that removal of Ag reverses exhaustion. Although programmed death I was up-regulated on chronic Ag-stimulated CD8(+) T cells, it played no role in the exhaustion. These findings provide a novel insight into the mechanisms that control functional exhaustion of CD8(+) T cells in chronic infection. The Journal of Immunology, 2009, 182: 6697-6708.
Original languageEnglish
Pages (from-to)6697-6708
Number of pages12
JournalJournal of Immunology
Volume182
Issue number11
DOIs
Publication statusPublished - 1 Jun 2009
Externally publishedYes

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