Abstract
During chronic infection, pathogen-specific CD8(+) T cells upregulate expression of molecules such as the inhibitory surface receptor PD-1, have diminished cytokine production and are thought to undergo terminal differentiation into exhausted cells. Here we found that T cells with memory-like properties were generated during chronic infection. After transfer into naive mice, these cells robustly proliferated and controlled a viral infection. The reexpanded T cell populations continued to have the exhausted phenotype they acquired during the chronic infection. Thus, the cells underwent a form of differentiation that was stably transmitted to daughter cells. We therefore propose that during persistent infection, effector T cells stably differentiate into a state that is optimized to limit viral replication without causing overwhelming immunological pathology.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, Viral / immunology*
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Cell Proliferation*
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Chronic Disease
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Flow Cytometry
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Host-Pathogen Interactions / immunology
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Humans
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Immunologic Memory / genetics
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Immunologic Memory / immunology*
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Immunophenotyping
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Lymphocytic Choriomeningitis / genetics
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Lymphocytic Choriomeningitis / immunology
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Lymphocytic Choriomeningitis / virology
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Lymphocytic choriomeningitis virus / immunology
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Lymphocytic choriomeningitis virus / physiology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Programmed Cell Death 1 Receptor / genetics
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Programmed Cell Death 1 Receptor / immunology
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Programmed Cell Death 1 Receptor / metabolism
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Receptors, Antigen, T-Cell, alpha-beta / genetics
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Receptors, Antigen, T-Cell, alpha-beta / immunology
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Receptors, Antigen, T-Cell, alpha-beta / metabolism
Substances
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Antigens, Viral
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Programmed Cell Death 1 Receptor
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Receptors, Antigen, T-Cell, alpha-beta