Journal article
Chronic Antigen Stimulation Alone Is Sufficient to Drive CD8(+) T Cell Exhaustion
The Journal of immunology (1950), v 182(11), pp 6697-6708
01 Jun 2009
PMID: 19454664
Featured in Collection : UN Sustainable Development Goals @ Drexel
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.
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Details
- Title
- Chronic Antigen Stimulation Alone Is Sufficient to Drive CD8(+) T Cell Exhaustion
- Creators
- Christine M. Bucks - Drexel UniversityJillian A. Norton - Drexel Univ, Coll Med, Dept Microbiol & Immunol, Philadelphia, PA 19129 USAAlina C. Boesteanu - Drexel UniversityYvonne M. Mueller - Drexel UniversityPeter D. Katsikis - Drexel Univ, Coll Med, Dept Microbiol & Immunol, Philadelphia, PA 19129 USA
- Publication Details
- The Journal of immunology (1950), v 182(11), pp 6697-6708
- Publisher
- American Association of Immunologists
- Number of pages
- 12
- Grant note
- R01 AI62437; R01 AI46719; R01 AI66215 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R56AI046719 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID)
- Resource Type
- Journal article
- Language
- English
- Web of Science ID
- WOS:000266258300011
- Scopus ID
- 2-s2.0-67449135849
- Other Identifier
- 991019339575904721
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- Web of Science research areas
- Immunology