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

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

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)566-581
Number of pages16
JournalEuropean Journal of Immunology
Volume52
Issue number4
Early online date12 Feb 2022
DOIs
Publication statusPublished - Apr 2022

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