Abstract
The hallmark of chronic viral infections is a progressive exhaustion of antigen-specific CD8(+) T cells that leads to persisting viral replication. It is generally believed that exhaustion is a consequence of the accumulation of multiple inhibitory receptors on CD8(+) T cells that makes them dysfunctional. Here, we show that during human chronic HIV-1 infection, a CD8(+) T-cell positive costimulatory pathway mediated by DNAX-activating molecule-1 is also disrupted. Thus, DNAX-activating molecule-1 downregulation on CD8(+) T cells aggravates the impairment of CTL effector function in chronic HIV-1 infection.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, CD / physiology
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Antigens, Differentiation, T-Lymphocyte / biosynthesis
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Antigens, Differentiation, T-Lymphocyte / genetics
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Antigens, Differentiation, T-Lymphocyte / immunology*
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Antigens, Viral / immunology
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Apoptosis Regulatory Proteins / physiology
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / pathology*
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Down-Regulation
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Glycoproteins / immunology
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HIV Infections / immunology*
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HIV Infections / virology
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HIV-1 / immunology
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HIV-1 / physiology*
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Humans
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Lymphocyte Activation
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Lymphocyte Count
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Lymphocytic Choriomeningitis / immunology
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Mice
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Peptide Fragments / immunology
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Programmed Cell Death 1 Receptor
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Receptors, Virus / immunology
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T-Cell Antigen Receptor Specificity
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Viral Load
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Viral Proteins / immunology
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Virus Replication
Substances
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Antigens, CD
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Antigens, Differentiation, T-Lymphocyte
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Antigens, Viral
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Apoptosis Regulatory Proteins
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CD226 antigen
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Glycoproteins
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PDCD1 protein, human
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Peptide Fragments
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Programmed Cell Death 1 Receptor
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Receptors, Virus
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Viral Proteins
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glycoprotein peptide 33-41, Lymphocytic choriomeningitis virus
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poliovirus receptor