title: CD161+ MAIT cells are severely reduced in peripheral blood and lymph nodes of HIV-infected individuals independently of disease progression.
abstract: Mucosal-associated invariant T (MAIT) cells are characterized by the combined expression of the semi-invariant T cell receptor (TCR) Vα7.2, the lectin receptor CD161, as well as IL-18R, and play an important role in antibacterial host defense of the gut. The current study characterized CD161(+) MAIT and CD161-TCRVα7.2(+) T cell subsets within a large cohort of HIV patients with emphasis on patients with slow disease progression and elite controllers. Mononuclear cells from blood and lymph node samples as well as plasma from 63 patients and 26 healthy donors were analyzed by multicolor flow cytometry and ELISA for IL-18, sCD14 and sCD163. Additionally, MAIT cells were analyzed after in vitro stimulation with different cytokines and/or fixed E.coli. Reduced numbers of CD161(+) MAIT cells during HIV infection were detectable in the blood and lymph nodes of all patient groups, including elite controllers. CD161+ MAIT cell numbers did not recover even after successful antiretroviral treatment. The loss of CD161(+) MAIT cells was correlated with higher levels of MAIT cell activation; an increased frequency of the CD161-TCRVα7.2(+)T cell subset in HIV infection was observed. In vitro stimulation of MAIT cells with IL-18 and IL-12, IL-7 and fixed E.coli also resulted in a rapid and additive reduction of the MAIT cell frequency defined by CD161, IL-18R and CCR6. In summary, the irreversible reduction of the CD161(+) MAIT cell subset seems to be an early event in HIV infection that is independent of later stages of the disease. This loss appears to be at least partially due to the distinctive vulnerability of MAIT cells to the pronounced stimulation by microbial products and cytokines during HIV-infection.
authors.affiliation: Infectious Diseases Unit, Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Heinrich Pette Institute - Leibniz Institute for Experimental Virology, Hamburg, Germany.
authors.forename: Johanna Maria
authors.initials: JM
authors.lastname: Eberhard
authors.affiliation: Infectious Diseases Unit, Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Department of Oral and Maxillofacial Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Heinrich Pette Institute - Leibniz Institute for Experimental Virology, Hamburg, Germany.
authors.forename: Philip
authors.initials: P
authors.lastname: Hartjen
authors.affiliation: Infectious Diseases Unit, Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Heinrich Pette Institute - Leibniz Institute for Experimental Virology, Hamburg, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Kummer
authors.affiliation: Department of Immunology and Rheumatology, Hannover Medical School, Hanover, Germany; German Center for Infection Research (DZIF), partner site Hamburg and Hannover, Hamburg and Hannover, Germany.
authors.forename: Reinhold E
authors.initials: RE
authors.lastname: Schmidt
authors.affiliation: Department of General Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Bockhorn
authors.affiliation: Department of Internal Medicine I, University Hospital of Cologne, Cologne, Germany.
authors.forename: Clara
authors.initials: C
authors.lastname: Lehmann
authors.affiliation: School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Ashwin
authors.initials: A
authors.lastname: Balagopal
authors.affiliation: Heinrich Pette Institute - Leibniz Institute for Experimental Virology, Hamburg, Germany; German Center for Infection Research (DZIF), partner site Hamburg and Hannover, Hamburg and Hannover, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Hauber
authors.affiliation: Infectious Diseases Unit, Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Heinrich Pette Institute - Leibniz Institute for Experimental Virology, Hamburg, Germany; German Center for Infection Research (DZIF), partner site Hamburg and Hannover, Hamburg and Hannover, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: van Lunzen
authors.affiliation: Infectious Diseases Unit, Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Heinrich Pette Institute - Leibniz Institute for Experimental Virology, Hamburg, Germany; German Center for Infection Research (DZIF), partner site Hamburg and Hannover, Hamburg and Hannover, Germany.
authors.forename: Julian
authors.initials: J
authors.lastname: Schulze zur Wiesch
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use; D015703:Antigens, CD / Q000097:blood; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood; D018450:Disease Progression; D004926:Escherichia coli / Q000502:physiology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000473:pathology*; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology; D018664:Interleukin-12 / Q000378:metabolism / Q000494:pharmacology; D020382:Interleukin-18 / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D015851:Interleukin-7 / Q000378:metabolism / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors / Q000097:blood; D008198:Lymph Nodes / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000378:metabolism*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000097:blood; D053724:Receptors, Interleukin-18 / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D000098902:CD163 Antigen
chemical_list: D019380:Anti-HIV Agents; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D020382:Interleukin-18; D015851:Interleukin-7; D018950:Lipopolysaccharide Receptors; D055651:NK Cell Lectin-Like Receptor Subfamily B; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011956:Receptors, Cell Surface; D053724:Receptors, Interleukin-18; D018664:Interleukin-12