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PMID: 25437561 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

CD161 defines a transcriptional and functional phenotype across distinct human T cell lineages.

Cell reports ·Vol. 9 ·No. 3 ·2014-11-06 ·Pages 1075-88

Fergusson JR, Smith KE, Fleming VM, Rajoriya N, Newell EW, Simmons R, Marchi E, Björkander S, Kang YH, Swadling L, Kurioka A, Sahgal N, Lockstone H, Baban D, Freeman GJ, Sverremark-Ekström E, Davis MM, Davenport MP, Venturi V, Ussher JE, Willberg CB, Klenerman P

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.

MeSH Terms
Adult CD4-Positive T-Lymphocytes/cytology,drug effects,metabolism CD8-Positive T-Lymphocytes/cytology,drug effects,metabolism Cell Lineage/drug effects,immunology Humans Interleukin-12/pharmacology Interleukin-18/pharmacology Lymphocyte Activation/drug effects,immunology NK Cell Lectin-Like Receptor Subfamily B/metabolism Phenotype Principal Component Analysis Receptors, Antigen, T-Cell, alpha-beta/metabolism Receptors, Antigen, T-Cell, gamma-delta/metabolism T-Lymphocyte Subsets/cytology,drug effects,metabolism T-Lymphocytes/cytology,drug effects,metabolism Transcription, Genetic/drug effects
Chemicals
Interleukin-18 KLRB1 protein, human NK Cell Lectin-Like Receptor Subfamily B Receptors, Antigen, T-Cell, alpha-beta Receptors, Antigen, T-Cell, gamma-delta Interleukin-12
Authors & Affiliations
22 authors, click to expand affiliations / ORCID
Fergusson Joannah R
Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, UK.
Smith Kira E
Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, UK.
Fleming Vicki M
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.
Rajoriya Neil
Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, UK.
Newell Evan W
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.
Simmons Ruth
Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, UK.
Marchi Emanuele
Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, UK.
Björkander Sophia
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 106 91 Stockholm, Sweden.
Kang Yu-Hoi
Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, UK.
Swadling Leo
Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, UK.
Kurioka Ayako
Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, UK.
Sahgal Natasha
Bioinformatics and Statistical Genetics Core, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
Lockstone Helen
Bioinformatics and Statistical Genetics Core, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
Baban Dilair
Bioinformatics and Statistical Genetics Core, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
Freeman Gordon J
Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
Sverremark-Ekström Eva
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 106 91 Stockholm, Sweden.
Davis Mark M
Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA.
Davenport Miles P
Department of Haematology, Prince of Wales Hospital, Kensington, NSW NS2 2052, Australia.
Venturi Vanessa
Department of Haematology, Prince of Wales Hospital, Kensington, NSW NS2 2052, Australia.
Ussher James E
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.
Willberg Christian B
Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, UK.
Klenerman Paul
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: [email protected].
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Article Info
Journal
Cell reports
Abbr.
Cell Rep
ISSN
2211-1247
DOI
10.1016/j.celrep.2014.09.045
Email
[email protected]
Published
2014-11-06
Epub
2014-00-23
Pages
1075-88
Language
English
Region
United States
NLM ID
101573691
PMCID
PMC4250839
Subset
IM
Grants
Wellcome Trust · WT091663MA · United Kingdom
NIAID NIH HHS · U19 AI057229 · United States
NIAID NIH HHS · U19AI 082630 · United States
Wellcome Trust · 091663 · United Kingdom
NIAID NIH HHS · U19 AI082630 · United States
Wellcome Trust · 092871/Z/10/Z · United Kingdom
Wellcome Trust · United Kingdom
Databases
GEO
GSE62099
External Links
PubMed source DOI: 10.1016/j.celrep.2014.09.045 PMC Full Text View journal details
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