title: CD161 defines a transcriptional and functional phenotype across distinct human T cell lineages.
abstract: The C-type lectin CD161 is expressed by a large proportion of human T lymphocytes of all lineages, including a population known as mucosal-associated invariant T (MAIT) cells. To understand whether different T cell subsets expressing CD161 have similar properties, we examined these populations in parallel using mass cytometry and mRNA microarray approaches. The analysis identified a conserved CD161++/MAIT cell transcriptional signature enriched in CD161+CD8+ T cells, which can be extended to CD161+ CD4+ and CD161+TCRγδ+ T cells. Furthermore, this led to the identification of a shared innate-like, TCR-independent response to interleukin (IL)-12 plus IL-18 by different CD161-expressing T cell populations. This response was independent of regulation by CD161, which acted as a costimulatory molecule in the context of T cell receptor stimulation. Expression of CD161 hence identifies a transcriptional and functional phenotype, shared across human T lymphocytes and independent of both T cell receptor (TCR) expression and cell lineage.
authors.affiliation: Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, UK.
authors.forename: Joannah R
authors.initials: JR
authors.lastname: Fergusson
authors.affiliation: Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, UK.
authors.forename: Kira E
authors.initials: KE
authors.lastname: Smith
authors.affiliation: Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, UK; Department of Microbiology and Infectious Disease, Oxford University Hospitals NHS Trust, Oxford OX3 9DU, UK.
authors.forename: Vicki M
authors.initials: VM
authors.lastname: Fleming
authors.affiliation: Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, UK.
authors.forename: Neil
authors.initials: N
authors.lastname: Rajoriya
authors.affiliation: Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA; Agency for Science, Technology and Research (A(∗)STAR), Singapore Immunology Network (SIgN), Singapore 138632, Singapore.
authors.forename: Evan W
authors.initials: EW
authors.lastname: Newell
authors.affiliation: Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, UK.
authors.forename: Ruth
authors.initials: R
authors.lastname: Simmons
authors.affiliation: Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, UK.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Marchi
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 106 91 Stockholm, Sweden.
authors.forename: Sophia
authors.initials: S
authors.lastname: Björkander
authors.affiliation: Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, UK.
authors.forename: Yu-Hoi
authors.initials: YH
authors.lastname: Kang
authors.affiliation: Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, UK.
authors.forename: Leo
authors.initials: L
authors.lastname: Swadling
authors.affiliation: Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, UK.
authors.forename: Ayako
authors.initials: A
authors.lastname: Kurioka
authors.affiliation: Bioinformatics and Statistical Genetics Core, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
authors.forename: Natasha
authors.initials: N
authors.lastname: Sahgal
authors.affiliation: Bioinformatics and Statistical Genetics Core, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
authors.forename: Helen
authors.initials: H
authors.lastname: Lockstone
authors.affiliation: Bioinformatics and Statistical Genetics Core, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
authors.forename: Dilair
authors.initials: D
authors.lastname: Baban
authors.affiliation: Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Gordon J
authors.initials: GJ
authors.lastname: Freeman
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 106 91 Stockholm, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Sverremark-Ekström
authors.affiliation: Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Davis
authors.affiliation: Department of Haematology, Prince of Wales Hospital, Kensington, NSW NS2 2052, Australia.
authors.forename: Miles P
authors.initials: MP
authors.lastname: Davenport
authors.affiliation: Department of Haematology, Prince of Wales Hospital, Kensington, NSW NS2 2052, Australia.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Venturi
authors.affiliation: Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, UK; Department of Microbiology and Immunology, University of Otago, Dunedin 9054, New Zealand.
authors.forename: James E
authors.initials: JE
authors.lastname: Ussher
authors.affiliation: Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, UK.
authors.forename: Christian B
authors.initials: CB
authors.lastname: Willberg
authors.affiliation: Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, UK; NIHR Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford OX3 9TU, UK. Electronic address: paul.klenerman@ndm.ox.ac.uk.
authors.forename: Paul
authors.initials: P
authors.lastname: Klenerman
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019070:Cell Lineage / Q000187:drug effects / Q000276:immunology; D006801:Humans; D018664:Interleukin-12 / Q000494:pharmacology; D020382:Interleukin-18 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000378:metabolism*; D010641:Phenotype; D025341:Principal Component Analysis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D020382:Interleukin-18; C527203:KLRB1 protein, human; D055651:NK Cell Lectin-Like Receptor Subfamily B; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018664:Interleukin-12