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Identification of phenotypically and functionally heterogeneous mouse mucosal-associated invariant T cells using MR1 tetramers
Studies on the biology of mucosal-associated invariant T cells (MAIT cells) in mice have been hampered by a lack of specific reagents. Using MR1-antigen (Ag) tetramers that specifically bind to the MR1-restricted MAIT T cell receptors (TCRs), we demonstrate that MAIT cells are detectable in a broad...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4493408/ https://www.ncbi.nlm.nih.gov/pubmed/26101265 http://dx.doi.org/10.1084/jem.20142110 |
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author | Rahimpour, Azad Koay, Hui Fern Enders, Anselm Clanchy, Rhiannon Eckle, Sidonia B.G. Meehan, Bronwyn Chen, Zhenjun Whittle, Belinda Liu, Ligong Fairlie, David P. Goodnow, Chris C. McCluskey, James Rossjohn, Jamie Uldrich, Adam P. Pellicci, Daniel G. Godfrey, Dale I. |
author_facet | Rahimpour, Azad Koay, Hui Fern Enders, Anselm Clanchy, Rhiannon Eckle, Sidonia B.G. Meehan, Bronwyn Chen, Zhenjun Whittle, Belinda Liu, Ligong Fairlie, David P. Goodnow, Chris C. McCluskey, James Rossjohn, Jamie Uldrich, Adam P. Pellicci, Daniel G. Godfrey, Dale I. |
author_sort | Rahimpour, Azad |
collection | PubMed |
description | Studies on the biology of mucosal-associated invariant T cells (MAIT cells) in mice have been hampered by a lack of specific reagents. Using MR1-antigen (Ag) tetramers that specifically bind to the MR1-restricted MAIT T cell receptors (TCRs), we demonstrate that MAIT cells are detectable in a broad range of tissues in C57BL/6 and BALB/c mice. These cells include CD4(−)CD8(−), CD4(−)CD8(+), and CD4(+)CD8(−) subsets, and their frequency varies in a tissue- and strain-specific manner. Mouse MAIT cells have a CD44(hi)CD62L(lo) memory phenotype and produce high levels of IL-17A, whereas other cytokines, including IFN-γ, IL-4, IL-10, IL-13, and GM-CSF, are produced at low to moderate levels. Consistent with high IL-17A production, most MAIT cells express high levels of retinoic acid–related orphan receptor γt (RORγt), whereas RORγt(lo) MAIT cells predominantly express T-bet and produce IFN-γ. Most MAIT cells express the promyelocytic leukemia zinc finger (PLZF) transcription factor, and their development is largely PLZF dependent. These observations contrast with previous reports that MAIT cells from Vα19 TCR transgenic mice are PLZF(−) and express a naive CD44(lo) phenotype. Accordingly, MAIT cells from normal mice more closely resemble human MAIT cells than previously appreciated, and this provides the foundation for further investigations of these cells in health and disease. |
format | Online Article Text |
id | pubmed-4493408 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-44934082015-12-29 Identification of phenotypically and functionally heterogeneous mouse mucosal-associated invariant T cells using MR1 tetramers Rahimpour, Azad Koay, Hui Fern Enders, Anselm Clanchy, Rhiannon Eckle, Sidonia B.G. Meehan, Bronwyn Chen, Zhenjun Whittle, Belinda Liu, Ligong Fairlie, David P. Goodnow, Chris C. McCluskey, James Rossjohn, Jamie Uldrich, Adam P. Pellicci, Daniel G. Godfrey, Dale I. J Exp Med Article Studies on the biology of mucosal-associated invariant T cells (MAIT cells) in mice have been hampered by a lack of specific reagents. Using MR1-antigen (Ag) tetramers that specifically bind to the MR1-restricted MAIT T cell receptors (TCRs), we demonstrate that MAIT cells are detectable in a broad range of tissues in C57BL/6 and BALB/c mice. These cells include CD4(−)CD8(−), CD4(−)CD8(+), and CD4(+)CD8(−) subsets, and their frequency varies in a tissue- and strain-specific manner. Mouse MAIT cells have a CD44(hi)CD62L(lo) memory phenotype and produce high levels of IL-17A, whereas other cytokines, including IFN-γ, IL-4, IL-10, IL-13, and GM-CSF, are produced at low to moderate levels. Consistent with high IL-17A production, most MAIT cells express high levels of retinoic acid–related orphan receptor γt (RORγt), whereas RORγt(lo) MAIT cells predominantly express T-bet and produce IFN-γ. Most MAIT cells express the promyelocytic leukemia zinc finger (PLZF) transcription factor, and their development is largely PLZF dependent. These observations contrast with previous reports that MAIT cells from Vα19 TCR transgenic mice are PLZF(−) and express a naive CD44(lo) phenotype. Accordingly, MAIT cells from normal mice more closely resemble human MAIT cells than previously appreciated, and this provides the foundation for further investigations of these cells in health and disease. The Rockefeller University Press 2015-06-29 /pmc/articles/PMC4493408/ /pubmed/26101265 http://dx.doi.org/10.1084/jem.20142110 Text en © 2015 Rahimpour et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Article Rahimpour, Azad Koay, Hui Fern Enders, Anselm Clanchy, Rhiannon Eckle, Sidonia B.G. Meehan, Bronwyn Chen, Zhenjun Whittle, Belinda Liu, Ligong Fairlie, David P. Goodnow, Chris C. McCluskey, James Rossjohn, Jamie Uldrich, Adam P. Pellicci, Daniel G. Godfrey, Dale I. Identification of phenotypically and functionally heterogeneous mouse mucosal-associated invariant T cells using MR1 tetramers |
title | Identification of phenotypically and functionally heterogeneous mouse mucosal-associated invariant T cells using MR1 tetramers |
title_full | Identification of phenotypically and functionally heterogeneous mouse mucosal-associated invariant T cells using MR1 tetramers |
title_fullStr | Identification of phenotypically and functionally heterogeneous mouse mucosal-associated invariant T cells using MR1 tetramers |
title_full_unstemmed | Identification of phenotypically and functionally heterogeneous mouse mucosal-associated invariant T cells using MR1 tetramers |
title_short | Identification of phenotypically and functionally heterogeneous mouse mucosal-associated invariant T cells using MR1 tetramers |
title_sort | identification of phenotypically and functionally heterogeneous mouse mucosal-associated invariant t cells using mr1 tetramers |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4493408/ https://www.ncbi.nlm.nih.gov/pubmed/26101265 http://dx.doi.org/10.1084/jem.20142110 |
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