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

T-bet is the lineage-specifying transcription factor for CD4+ T helper type 1 (TH 1) cells. T-bet has also been found in other CD4+ T cell subsets, including TH 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 a naïve cell 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 polarised to the TH 1 lineage, predisposed to produce IFNγ upon cell activation, and resist repolarisation to other lineages in vitro and in vivo. These results demonstrate that lineage-specifying factors can polarise T cells in the absence of canonical markers of T cell activation and that this has an impact on the subsequent T helper response. This article is protected by copyright. All rights reserved.