title: Early and nonreversible decrease of CD161++ /MAIT cells in HIV infection.
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.
authors.affiliation: National Institute for Health Research Biomedical Research Centre, University of Oxford, Oxford, UK. pcosgrove@partners.org
authors.forename: Cormac
authors.initials: C
authors.lastname: Cosgrove
authors.forename: James E
authors.initials: JE
authors.lastname: Ussher
authors.forename: Andri
authors.initials: A
authors.lastname: Rauch
authors.forename: Kathleen
authors.initials: K
authors.lastname: Gärtner
authors.forename: Ayako
authors.initials: A
authors.lastname: Kurioka
authors.forename: Michael H
authors.initials: MH
authors.lastname: Hühn
authors.forename: Krista
authors.initials: K
authors.lastname: Adelmann
authors.forename: Yu-Hoi
authors.initials: YH
authors.lastname: Kang
authors.forename: Joannah R
authors.initials: JR
authors.lastname: Fergusson
authors.forename: Peter
authors.initials: P
authors.lastname: Simmonds
authors.forename: Philip
authors.initials: P
authors.lastname: Goulder
authors.forename: Ted H
authors.initials: TH
authors.lastname: Hansen
authors.forename: Julie
authors.initials: J
authors.lastname: Fox
authors.forename: Huldrych F
authors.initials: HF
authors.lastname: Günthard
authors.forename: Nina
authors.initials: N
authors.lastname: Khanna
authors.forename: Fiona
authors.initials: F
authors.lastname: Powrie
authors.forename: Alan
authors.initials: A
authors.lastname: Steel
authors.forename: Brian
authors.initials: B
authors.lastname: Gazzard
authors.forename: Rodney E
authors.initials: RE
authors.lastname: Phillips
authors.forename: John
authors.initials: J
authors.lastname: Frater
authors.forename: Holm
authors.initials: H
authors.lastname: Uhlig
authors.forename: Paul
authors.initials: P
authors.lastname: Klenerman
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D017209:Apoptosis / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D002478:Cells, Cultured; D015331:Cohort Studies; D004926:Escherichia coli / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006678:HIV / Q000187:drug effects / Q000276:immunology; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology*; D007150:Immunohistochemistry; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism / Q000821:virology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000276:immunology* / Q000378:metabolism; D019713:Receptors, CCR5 / Q000276:immunology / Q000378:metabolism; D054399:Receptors, CCR6 / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D013997:Time Factors
chemical_list: D019380:Anti-HIV Agents; C106311:CCR6 protein, human; D020381:Interleukin-17; C527203:KLRB1 protein, human; D055651:NK Cell Lectin-Like Receptor Subfamily B; D019713:Receptors, CCR5; D054399:Receptors, CCR6