Abstract
Cytotoxic T lymphocytes (CTLs) are killer cells that are crucial in the control of viral pathogens and cancers. They can become exhausted during chronic viral infection, a phenomenon that consists of a reduction in both number and functionality of CTLs. Recently, Barber and colleagues demonstrated that B7-H1 (also called PD-L1), a cell-surface molecule that is widely distributed in tissues, was necessary for the maintenance of T-cell exhaustion in a chronic-infection mouse model of lymphocytic choriomeningitis virus (LCMV). PD-1, the receptor of B7-H1, was greatly upregulated on CTLs in response to LCMV, and its expression was maintained during chronic infection. Blockade of the B7-H1-PD-1 pathway by a monoclonal antibody restored CTL function and reduced viral burden. These results suggest a new strategy for the treatment of chronic viral infection.
MeSH terms
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Animals
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Antibodies
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Antigens, Differentiation / genetics
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Antigens, Differentiation / metabolism*
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B7-1 Antigen / genetics
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B7-1 Antigen / immunology
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B7-1 Antigen / metabolism*
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B7-H1 Antigen
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CD8-Positive T-Lymphocytes / cytology
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CD8-Positive T-Lymphocytes / immunology*
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Cell Proliferation
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Chronic Disease
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Gene Expression Regulation
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Lymphocytic Choriomeningitis / genetics
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Lymphocytic Choriomeningitis / immunology*
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Lymphocytic Choriomeningitis / metabolism
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Lymphocytic choriomeningitis virus / immunology
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / immunology
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Membrane Glycoproteins / metabolism*
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Mice
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Mice, Knockout
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Peptides / genetics
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Peptides / immunology
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Peptides / metabolism*
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Programmed Cell Death 1 Receptor
Substances
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Antibodies
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Antigens, Differentiation
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B7-1 Antigen
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B7-H1 Antigen
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Cd274 protein, mouse
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Membrane Glycoproteins
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Pdcd1 protein, mouse
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Peptides
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Programmed Cell Death 1 Receptor