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CD161intCD8+T cells: a novel population of highly functional, memory CD8+T cells enriched within the gut

Lookup NU author(s): Dr Lucy Walker

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Abstract

The C-type lectin-like receptor CD161 is expressed by lymphocytes found in human gut and liver, as well as blood, especially natural killer (NK) cells, T helper 17 (Th17) cells, and a population of unconventional Tcells known as mucosalassociated invariant T (MAIT) cells. The association of high CD161 expression with innate T-cell populations including MAITcells is established. Here we show that CD161 is also expressed, at intermediate levels, on a prominent subset of polyclonal CD8+ T cells, including antiviral populations that display a memory phenotype. These memory CD161(int)CD8+ Tcells are enriched within the colon and express both CD103 and CD69, markers associated with tissue residence. Furthermore, this population was characterized by enhanced polyfunctionality, increased levels of cytotoxic mediators, and high expression of the transcription factors T-bet and eomesodermin (EOMES). Such populations were induced by novel vaccine strategies based on adenoviral vectors, currently in trial against hepatitis C virus. Thus, intermediate CD161 expression marks potent polyclonal, polyfunctional tissue-homing CD8+ T-cell populations in humans. As induction of such responses represents a major aim of T-cell prophylactic and therapeutic vaccines in viral disease and cancer, analysis of these populations could be of value in the future.


Publication metadata

Author(s): Fergusson JR, Hühn MH, Swadling L, Walker LJ, Kurioka A, Llibre A, Bertoletti A, Hollander G, Newell EW, Davis MM, Sverremark-Ekstrom E, Powrie F, Capone S, Folgori A, Barnes E, Willberg CB, Ussher JE, Klenerman P

Publication type: Article

Publication status: Published

Journal: Mucosal Immunology

Year: 2016

Volume: 9

Issue: 2

Pages: 401-413

Print publication date: 01/03/2016

Online publication date: 29/07/2015

Acceptance date: 13/06/2015

ISSN (print): 1933-0219

ISSN (electronic): 1935-3456

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/mi.2015.69

DOI: 10.1038/mi.2015.69


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Funding

Funder referenceFunder name
Medical Research Council
Oxford Dominions Trust
James Martin School for the 21st Century (Oxford)
NIHR Biomedical Research Centre
NIHR Biomedical Research Centre (Oxford)
Nuffield Department of Clinical Medicine (Oxford)
092871/Z/10/ZWellcome Trust IITM Programme
U19AI082630NIH (NIAD)
WT091663MAWellcome Trust

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