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

1. Cell Rep. 2014 Nov 6;9(3):1075-88. doi: 10.1016/j.celrep.2014.09.045. Epub 2014 Oct 23. CD161 defines a transcriptional and functional phenotype across distinct human T cell lineages. Fergusson JR(1), Smith KE(1), Fleming VM(2), Rajoriya N(1), Newell EW(3), Simmons R(1), Marchi E(1), Björkander S(4), Kang YH(1), Swadling L(1), Kurioka A(1), Sahgal N(5), Lockstone H(5), Baban D(5), Freeman GJ(6), Sverremark-Ekström E(4), Davis MM(7), Davenport MP(8), Venturi V(8), Ussher JE(9), Willberg CB(1), Klenerman P(10). Author information: (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. 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. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved. DOI: 10.1016/j.celrep.2014.09.045 PMCID: PMC4250839 PMID: 25437561 [Indexed for MEDLINE]