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

Joannah R Fergusson; Kira E Smith; Vicki M Fleming; Neil Rajoriya; Evan W Newell; Ruth Simmons; Emanuele Marchi; Sophia Björkander; Yu-Hoi Kang; Leo Swadling; Ayako Kurioka; Natasha Sahgal; Helen Lockstone; Dilair Baban; Gordon J Freeman; Eva Sverremark-Ekström; Mark M Davis; Miles P Davenport; Vanessa Venturi; James E Ussher; Christian B Willberg; Paul Klenerman

doi:10.1016/j.celrep.2014.09.045

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

Cell Rep. 2014 Nov 6;9(3):1075-88. doi: 10.1016/j.celrep.2014.09.045. Epub 2014 Oct 23.

Authors

Joannah R Fergusson¹, Kira E Smith¹, Vicki M Fleming², Neil Rajoriya¹, Evan W Newell³, Ruth Simmons¹, Emanuele Marchi¹, Sophia Björkander⁴, Yu-Hoi Kang¹, Leo Swadling¹, Ayako Kurioka¹, Natasha Sahgal⁵, Helen Lockstone⁵, Dilair Baban⁵, Gordon J Freeman⁶, Eva Sverremark-Ekström⁴, Mark M Davis⁷, Miles P Davenport⁸, Vanessa Venturi⁸, James E Ussher⁹, Christian B Willberg¹, Paul Klenerman¹⁰

Affiliations

¹ Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, UK.
² 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.
³ 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.
⁴ Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 106 91 Stockholm, Sweden.
⁵ Bioinformatics and Statistical Genetics Core, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
⁶ Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
⁷ Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA.
⁸ Department of Haematology, Prince of Wales Hospital, Kensington, NSW NS2 2052, Australia.
⁹ 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.
¹⁰ 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.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
CD4-Positive T-Lymphocytes / cytology
CD4-Positive T-Lymphocytes / drug effects
CD4-Positive T-Lymphocytes / metabolism
CD8-Positive T-Lymphocytes / cytology
CD8-Positive T-Lymphocytes / drug effects
CD8-Positive T-Lymphocytes / metabolism
Cell Lineage* / drug effects
Cell Lineage* / immunology
Humans
Interleukin-12 / pharmacology
Interleukin-18 / pharmacology
Lymphocyte Activation / drug effects
Lymphocyte Activation / 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
T-Lymphocyte Subsets / drug effects
T-Lymphocyte Subsets / metabolism
T-Lymphocytes / cytology*
T-Lymphocytes / drug effects
T-Lymphocytes / metabolism*
Transcription, Genetic* / drug effects

Substances

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

Associated data

GEO/GSE62099

Abstract

Publication types

MeSH terms

Substances

Associated data

Grants and funding