Unique and Common Features of Innate-Like Human Vδ2+ γδT Cells and Mucosal-Associated Invariant T Cells.
| Title: | Unique and Common Features of Innate-Like Human Vδ2+ γδT Cells and Mucosal-Associated Invariant T Cells. |
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| Authors: | Provine NM; Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.; Binder B; Department of Internal Medicine II, University Hospital Freiburg, Freiburg, Germany.; FitzPatrick MEB; Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.; Schuch A; Department of Internal Medicine II, University Hospital Freiburg, Freiburg, Germany.; Faculty of Biology, University of Freiburg, Freiburg, Germany.; Garner LC; Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.; Williamson KD; Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.; van Wilgenburg B; Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom.; Thimme R; Department of Internal Medicine II, University Hospital Freiburg, Freiburg, Germany.; Klenerman P; Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.; Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom.; Hofmann M; Department of Internal Medicine II, University Hospital Freiburg, Freiburg, Germany. |
| Source: | Frontiers in immunology [Front Immunol] 2018 Apr 23; Vol. 9, pp. 756. Date of Electronic Publication: 2018 Apr 23 (Print Publication: 2018). |
| Publication Type: | Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Print ISSN: 1664-3224 (Print) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [Lausanne : Frontiers Research Foundation] |
| MeSH Terms: | Lymphocyte Activation/*immunology ; Mucosal-Associated Invariant T Cells/*immunology ; T-Lymphocyte Subsets/*immunology; Hepatitis C, Chronic/immunology ; Receptors, Antigen, T-Cell, gamma-delta/immunology ; Adult ; Female ; Humans ; Male ; Middle Aged |
| Abstract: | Mucosal-associated invariant T (MAIT) cells are innate-like T cells abundant in humans that can be activated in a TCR-independent manner by inflammatory and antiviral cytokines. In humans, the capacity for TCR-independent activation is functionally linked to a transcriptional program that can be identified by the expression of the C-type lectin receptor, CD161. In addition to MAIT cells, it has been demonstrated that a subset of γδT cells expresses CD161 and can be activated by TCR-independent cytokine stimulation. In this study, we sought to clarify the nature of cytokine-responsive human γδT cells. We could link CD161 expression on Vδ2+ versus Vδ1+ γδT cells to the observation that Vδ2+ γδT cells, but not Vδ1+ γδT cells, robustly produced IFN-γ upon stimulation with a variety of cytokine combinations. Interestingly, both CD161+ and CD161- Vδ2+ γδT cells responded to these stimuli, with increased functionality within the CD161+ subset. This innate-like responsiveness corresponded to high expression of PLZF and IL-18Rα, analogous to MAIT cells. Vδ2+ γδT cells in human duodenum and liver maintained a CD161+ IL-18Rα+ phenotype and produced IFN-γ in response to IL-12 and IL-18 stimulation. In contrast to MAIT cells, we could not detect IL-17A production but observed higher steady-state expression of Granzyme B by Vδ2+ γδT cells. Finally, we investigated the frequency and functionality of γδT cells in the context of chronic hepatitis C virus infection, as MAIT cells are reduced in frequency in this disease. By contrast, Vδ2+ γδT cells were maintained in frequency and displayed unimpaired IFN-γ production in response to cytokine stimulation. In sum, human Vδ2+ γδT cells are a functionally distinct population of cytokine-responsive innate-like T cells that is abundant in blood and tissues with similarities to human MAIT cells. |
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| Grant Information: | WT109965MA United Kingdom WT_ Wellcome Trust; 200154/Z/15/Z United Kingdom WT_ Wellcome Trust; United Kingdom MRC_ Medical Research Council; 109028/Z/15/Z United Kingdom WT_ Wellcome Trust; 109965/Z/15/Z United Kingdom WT_ Wellcome Trust |
| Contributed Indexing: | Keywords: Vδ2 γδ T cells; hepatitis C virus; innate-like T cells; mucosal immunology; mucosal-associated invariant T; γδ T cells |
| Substance Nomenclature: | 0 (Receptors, Antigen, T-Cell, gamma-delta) |
| Entry Date(s): | Date Created: 20180510 Date Completed: 20190607 Latest Revision: 20220216 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC5924964 |
| DOI: | 10.3389/fimmu.2018.00756 |
| PMID: | 29740432 |
| Database: | MEDLINE |
Journal Article; Research Support, Non-U.S. Gov't