CD161(int)CD8+ T cells: a novel population of highly functional, memory CD8+ T cells enriched within the gut.

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 T cells known as mucosal-associated invariant T (MAIT) cells. The association of high CD161 expression with innate T-cell populations including MAIT cells 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+ T cells 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.

• Authors: J R Fergusson, M H Hühn, L Swadling, L J Walker, A Kurioka, A Llibre, A Bertoletti, G Holländer, E W Newell, M M Davis, E Sverremark-Ekström, F Powrie, S Capone, A Folgori, E Barnes, C B Willberg, J E Ussher, P Klenerman
• Journal: Mucosal immunology (Mucosal Immunol) Vol. 9 Issue 2 Pg. 401-13 (Mar 2016) ISSN: 1935-3456 [Electronic] United States
• PMID: 26220166 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD
• Antigens, Differentiation, T-Lymphocyte
• CD69 antigen
• EOMES protein, human
• Integrin alpha Chains
• KLRB1 protein, human
• Lectins, C-Type
• NK Cell Lectin-Like Receptor Subfamily B
• T-Box Domain Proteins
• T-box transcription factor TBX21
• alpha E integrins
• Tetradecanoylphorbol Acetate

Topics

• Adenoviridae (immunology)
• Antigens, CD (genetics, immunology)
• Antigens, Differentiation, T-Lymphocyte (genetics, immunology)
• CD8-Positive T-Lymphocytes (drug effects, immunology, pathology)
• Clinical Trials as Topic
• Colitis, Ulcerative (genetics, immunology, pathology)
• Colon (immunology, pathology)
• Crohn Disease (genetics, immunology, pathology)
• Gene Expression Regulation
• Hepacivirus (immunology)
• Hepatitis C (immunology, prevention & control, virology)
• Humans
• Immunologic Memory
• Integrin alpha Chains (genetics, immunology)
• Intestinal Mucosa (immunology, pathology)
• Killer Cells, Natural (drug effects, immunology, pathology)
• Lectins, C-Type (genetics, immunology)
• Lymphocyte Activation
• NK Cell Lectin-Like Receptor Subfamily B (genetics, immunology)
• Primary Cell Culture
• Signal Transduction
• T-Box Domain Proteins (genetics, immunology)
• Tetradecanoylphorbol Acetate (pharmacology)
• Th17 Cells (drug effects, immunology, pathology)