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A population of naive-like CD4+ T cells stably polarized to the TH1 lineage

Research output: Contribution to journalArticlepeer-review

Jon Lo, Maria Vila de Mucha, Stephen Henderson, Luke Roberts, Laura Constable, Natividad Garrido Mesa, Arnulf Hertweck, Emilie Stolarczyk, Emma L Houlder, Ian Jackson, Andrew S. MacDonald, Nick Powell, Joana F Neves, Jane Howard, Richard Jenner, Graham Lord

Original languageEnglish
Pages (from-to)566-581
Number of pages16
JournalEuropean Journal of Immunology
Issue number4
Early online date12 Feb 2022
E-pub ahead of print12 Feb 2022
PublishedApr 2022

Bibliographical note

Funding Information: This study was supported by grants awarded by the Medical Research Council (MRC) to RGJ and GML (grant numbers MR/M003493/1 and MR/R001413/1), a CRUK PhD studentship supporting MVdM awarded to RGJ, an MRC grant (MR/K002996/1l), and a Wellcome Trust Advanced Fellowship awarded to JKH, a Marie Skłodowska‐Curie Fellowship awarded to JFN, and the CRUK UCL Centre (award C416/A25145) supporting SH. NP was funded by the Wellcome Trust (WT101159) and the Imperial National Institute for Health Research (NIHR) Biomedical Research Centre (BRC). Research was also supported by the BRC Flow Core facility at Guy's and St. Thomas’ NHS Foundation Trust and the MRC Flowcore at Imperial College London Hammersmith. RNA‐seq was performed by Paola Niola at UCL Genomics. Provision of T‐bet mice from Manchester was supported by Emma L. Houlder and Professor Andrew S. MacDonald. FM Publisher Copyright: © 2022 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.

King's Authors


T-bet is the lineage-specifying transcription factor for CD4 + T H1 cells. T-bet has also been found in other CD4 + T cell subsets, including T H17 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 T H1 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.

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