title: CD161(int)CD8+ T cells: a novel population of highly functional, memory CD8+ T cells enriched within the gut.
abstract: The C-type lectin-like receptor CD161 is expressed by lymphocytes found in human gut and liver, as well as blood, especially natural killer (NK) cells, T helper 17 (Th17) cells, and a population of unconventional T cells known as mucosal-associated invariant T (MAIT) cells. The association of high CD161 expression with innate T-cell populations including MAIT cells is established. Here we show that CD161 is also expressed, at intermediate levels, on a prominent subset of polyclonal CD8+ T cells, including antiviral populations that display a memory phenotype. These memory CD161(int)CD8+ T cells are enriched within the colon and express both CD103 and CD69, markers associated with tissue residence. Furthermore, this population was characterized by enhanced polyfunctionality, increased levels of cytotoxic mediators, and high expression of the transcription factors T-bet and eomesodermin (EOMES). Such populations were induced by novel vaccine strategies based on adenoviral vectors, currently in trial against hepatitis C virus. Thus, intermediate CD161 expression marks potent polyclonal, polyfunctional tissue-homing CD8+ T-cell populations in humans. As induction of such responses represents a major aim of T-cell prophylactic and therapeutic vaccines in viral disease and cancer, analysis of these populations could be of value in the future.
authors.affiliation: Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
authors.forename: J R
authors.initials: JR
authors.lastname: Fergusson
authors.affiliation: Translational Gastroenterology Unit, Nuffield Department of Clinical Medicine, Experimental Medicine Division, John Radcliffe Hospital, University of Oxford, Oxford, UK.
authors.forename: M H
authors.initials: MH
authors.lastname: Hühn
authors.affiliation: Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
authors.forename: L
authors.initials: L
authors.lastname: Swadling
authors.affiliation: Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.|Newcastle University Institute of Cellular Medicine, Newcastle upon Tyne, UK.
authors.forename: L J
authors.initials: LJ
authors.lastname: Walker
authors.affiliation: Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
authors.forename: A
authors.initials: A
authors.lastname: Kurioka
authors.affiliation: Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
authors.forename: A
authors.initials: A
authors.lastname: Llibre
authors.affiliation: Program Emerging Infectious Diseases, Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: A
authors.initials: A
authors.lastname: Bertoletti
authors.affiliation: Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
authors.forename: G
authors.initials: G
authors.lastname: Holländer
authors.affiliation: Department of Microbiology and Immunology, Stanford University, Stanford, California, USA.|Agency for Science, Technology and Research (A*STAR), Singapore Immunology Network (SIgN), Singapore, Singapore.
authors.forename: E W
authors.initials: EW
authors.lastname: Newell
authors.affiliation: Agency for Science, Technology and Research (A*STAR), Singapore Immunology Network (SIgN), Singapore, Singapore.
authors.forename: M M
authors.initials: MM
authors.lastname: Davis
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Sverremark-Ekström
authors.affiliation: Translational Gastroenterology Unit, Nuffield Department of Clinical Medicine, Experimental Medicine Division, John Radcliffe Hospital, University of Oxford, Oxford, UK.|Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
authors.forename: F
authors.initials: F
authors.lastname: Powrie
authors.affiliation: Okairos, Pomezia, Rome, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Capone
authors.affiliation: Okairos, Pomezia, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Folgori
authors.affiliation: Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
authors.forename: E
authors.initials: E
authors.lastname: Barnes
authors.affiliation: Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
authors.forename: C B
authors.initials: CB
authors.lastname: Willberg
authors.affiliation: Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.|Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
authors.forename: J E
authors.initials: JE
authors.lastname: Ussher
authors.affiliation: Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.|NIHR Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK.
authors.forename: P
authors.initials: P
authors.lastname: Klenerman
mesh_terms: D000256:Adenoviridae / Q000276:immunology; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D002986:Clinical Trials as Topic; D003093:Colitis, Ulcerative / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D003106:Colon / Q000276:immunology / Q000473:pathology; D003424:Crohn Disease / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005786:Gene Expression Regulation; D016174:Hepacivirus / Q000276:immunology; D006526:Hepatitis C / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D006801:Humans; D007156:Immunologic Memory; D039001:Integrin alpha Chains / Q000235:genetics / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology* / Q000473:pathology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000235:genetics / Q000276:immunology*; D061251:Primary Cell Culture; D015398:Signal Transduction; D020825:T-Box Domain Proteins / Q000235:genetics / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D000098815:T-bet Transcription Factor; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D039001:Integrin alpha Chains; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D020825:T-Box Domain Proteins; D013755:Tetradecanoylphorbol Acetate; D000098815:T-bet Transcription Factor; D000099192:CD69 Antigens; C491199:EOMES protein, human; C527203:KLRB1 protein, human; C091367:alpha E integrins