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. UssherChristian B. Willberg, Paul Klenerman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

190 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1075-1088
Number of pages14
JournalCell Reports
Issue number3
Publication statusPublished - 2014
Externally publishedYes

Bibliographical note

Funding Information:
The authors would like to thank T. Hansen for the kind provision of the MR1-blocking antibody, N. Rust for sorting expertise, C. Marchant for technical support, and all members of the laboratory for helpful discussion and support. J.R.F is supported by the Wellcome Trust IITM Programme (092871/Z/10/Z). This work was also supported by the Wellcome Trust (WT091663MA), the Medical Research Council, the NIHR Biomedical Research Centre (Oxford), the Nuffield Department of Clinical Medicine (Oxford), the James Martin School for the 21 st Century (Oxford), the NIH (NIAD U19AI 082630), and the Oxford Dominions Trust.

Publisher Copyright:
© 2014 The Authors.


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