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

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.