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

Abstract

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.

Keywords: CD4 T cells; Gene regulation; IFNg; Immune regulation; T cells; T helper cells; T-bet; TH1; Transgenic models; colitis; mouse model; naive T cells.