A population of naive-like CD4 + T cells stably polarized to the T H 1 lineage

• Published in: European journal of immunology 2022-04, Vol.52 (4), p.566-581
• Main Authors: Lo, Jonathan W, de Mucha, Maria Vila, Henderson, Stephen, Roberts, Luke B, Constable, Laura E, Garrido-Mesa, Natividad, Hertweck, Arnulf, Stolarczyk, Emilie, Houlder, Emma L, Jackson, Ian, MacDonald, Andrew S, Powell, Nick, Neves, Joana F, Howard, Jane K, Jenner, Richard G, Lord, Graham M
• Format: Article
• Language: English
• Subjects: Animals; Cell Differentiation; Gene Expression Regulation; Lymphocyte Activation; Mice; T-Box Domain Proteins - genetics; T-Box Domain Proteins - metabolism; T-Lymphocytes, Regulatory - metabolism; Th1 Cells; Th17 Cells - metabolism; Th2 Cells
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.202149228

T-bet is the lineage-specifying transcription factor for CD4 T 1 cells. T-bet has also been found in other CD4 T cell subsets, including T 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 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.