Abstract
HIV infection is associated with immune dysfunction, perturbation of immune-cell subsets and opportunistic infections. CD161++ CD8+ T cells are a tissue-infiltrating population that produce IL17A, IL22, IFN, and TNFα, cytokines important in mucosal immunity. In adults they dominantly express the semi-invariant TCR Vα7.2, the canonical feature of mucosal associated invariant T (MAIT) cells and have been recently implicated in host defense against pathogens. We analyzed the frequency and function of CD161++ /MAIT cells in peripheral blood and tissue from patients with early stage or chronic-stage HIV infection. We show that the CD161++ /MAIT cell population is significantly decreased in early HIV infection and fails to recover despite otherwise successful treatment. We provide evidence that CD161++ /MAIT cells are not preferentially infected but may be depleted through diverse mechanisms including accumulation in tissues and activation-induced cell death. This loss may impact mucosal defense and could be important in susceptibility to specific opportunistic infections in HIV.
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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Adult
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Anti-HIV Agents / therapeutic use
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Antiretroviral Therapy, Highly Active
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Apoptosis / immunology
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / metabolism
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CD8-Positive T-Lymphocytes / virology
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Cells, Cultured
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Cohort Studies
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Escherichia coli / immunology
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Female
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Flow Cytometry
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HIV / drug effects
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HIV / immunology
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HIV Infections / blood
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HIV Infections / drug therapy
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HIV Infections / immunology*
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Humans
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Immunity, Mucosal / immunology*
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Immunohistochemistry
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Interleukin-17 / immunology
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Interleukin-17 / metabolism
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Leukocytes, Mononuclear / immunology
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Leukocytes, Mononuclear / metabolism
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Leukocytes, Mononuclear / virology
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Lymphocyte Count
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Male
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Middle Aged
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NK Cell Lectin-Like Receptor Subfamily B / immunology*
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NK Cell Lectin-Like Receptor Subfamily B / metabolism
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Receptors, CCR5 / immunology
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Receptors, CCR5 / metabolism
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Receptors, CCR6 / immunology
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Receptors, CCR6 / metabolism
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / metabolism
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T-Lymphocyte Subsets / virology
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Time Factors
Substances
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Anti-HIV Agents
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CCR6 protein, human
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Interleukin-17
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KLRB1 protein, human
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NK Cell Lectin-Like Receptor Subfamily B
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Receptors, CCR5
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Receptors, CCR6