Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 52, Issue 4, Pages 566-581Publisher
WILEY
DOI: 10.1002/eji.202149228
Keywords
CD4 T cells; Gene regulation; Immune regulation; T helper cells; Transgenic models; T cells; T-bet; naive T cells; TH1; mouse model; colitis; IFNg
Categories
Funding
- Medical Research Council (MRC) [MR/M003493/1, MR/R001413/1]
- CRUK PhD studentship supporting MVdM
- MRC [MR/K002996/1l]
- Wellcome Trust Advanced Fellowship
- CRUK UCL Centre [C416/A25145]
- Wellcome Trust [WT101159]
- Imperial National Institute for Health Research (NIHR) Biomedical Research Centre (BRC)
- BRC Flow Core facility at Guy's and St. Thomas' NHS Foundation Trust
- MRC Flowcore at Imperial College London Hammersmith
- Marie Skodowska-Curie Fellowship
- MRC [MR/R001413/1] Funding Source: UKRI
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This study demonstrates the expression of T-bet in a subset of CD4(+) T cells with naive cell characteristics, and shows that these T-bet-expressing cells have distinct phenotypic and functional properties from previously described cell subsets. Naive-like T-bet-experienced cells are polarized to the T(H)1 lineage and resist repolarization to other lineages.
T-bet is the lineage-specifying transcription factor for CD4(+) T(H)1 cells. T-bet has also been found in other CD4(+) T cell subsets, including T(H)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 naive cell surface markers and transcriptional profile and that this novel cell population is phenotypically and functionally distinct from previously described populations of naive and memory CD4(+) T cells. Naive-like T-bet-experienced cells are polarized to the T(H)1 lineage, predisposed to produce IFN-gamma 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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