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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.

Type

Journal article

Journal

Blood

Publication Date

02/2013

Volume

121

Pages

951 - 961

Addresses

National Institute for Health Research Biomedical Research Centre, University of Oxford, Oxford, UK. pcosgrove@partners.org

Keywords

Leukocytes, Mononuclear, T-Lymphocyte Subsets, CD8-Positive T-Lymphocytes, Cells, Cultured, Humans, Escherichia coli, HIV, HIV Infections, Receptors, CCR5, Interleukin-17, Anti-HIV Agents, Lymphocyte Count, Antiretroviral Therapy, Highly Active, Flow Cytometry, Immunohistochemistry, Cohort Studies, Apoptosis, Immunity, Mucosal, Time Factors, Adult, Middle Aged, Female, Male, Receptors, CCR6, NK Cell Lectin-Like Receptor Subfamily B