Lo, Jonathan W;
de Mucha, Maria Vila;
Henderson, Stephen;
Roberts, Luke B;
Constable, Laura E;
Garrido-Mesa, Natividad;
Hertweck, Arnulf;
... Lord, Graham M; + view all
(2022)
A population of naive-like CD4+ T cells stably polarized to the TH 1 lineage.
European Journal of Immunology
10.1002/eji.202149228.
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Abstract
T-bet is the lineage-specifying transcription factor for CD4+ TH 1 cells. T-bet has also been found in other CD4+ T cell subsets, including TH 17 cells and Treg, where it modulates their functional characteristics. However, we lack information on when and where T-bet is expressed during T cell differentiation and how this impacts T cell differentiation and function. To address this, we traced the ontogeny of T-bet-expressing cells using a fluorescent fate-mapping mouse line. We demonstrate that T-bet is expressed in a subset of CD4+ T cells that have naïve cell surface markers and transcriptional profile and that this novel cell population is phenotypically and functionally distinct from previously described populations of naïve and memory CD4+ T cells. Naïve-like T-bet-experienced cells are polarized to the TH 1 lineage, predisposed to produce IFN-γ upon cell activation, and resist repolarization to other lineages in vitro and in vivo. These results demonstrate that lineage-specifying factors can polarize T cells in the absence of canonical markers of T cell activation and that this has an impact on the subsequent T-helper response.
| Type: | Article |
|---|---|
| Title: | A population of naive-like CD4+ T cells stably polarized to the TH 1 lineage |
| Location: | Germany |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/eji.202149228 |
| Publisher version: | https://doi.org/10.1002/eji.202149228 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | CD4 T cells, Gene regulation, IFNg, Immune regulation, T cells, T helper cells, T-bet, TH1, Transgenic models, colitis, mouse model, naive T cells |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10144298 |
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