A population of naive-like CD4 + T cells stably polarized to the T H 1 lineage.
Jonathan W LoMaria Vila de MuchaStephen HendersonLuke B RobertsLaura E ConstableNatividad Garrido-MesaArnulf HertweckEmilie StolarczykEmma L HoulderIan JacksonAndrew S MacDonaldNick PowellJoana F NevesJane K HowardRichard G JennerGraham M LordPublished in: European journal of immunology (2022)
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 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 H 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.
Keyphrases
- induced apoptosis
- single cell
- cell cycle arrest
- transcription factor
- high resolution
- cell death
- cell surface
- endoplasmic reticulum stress
- signaling pathway
- immune response
- bone marrow
- quantum dots
- dendritic cells
- working memory
- mesenchymal stem cells
- regulatory t cells
- high density
- fluorescent probe
- living cells
- cell fate
- wild type
- heat shock