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 naive cell surface markers and transcriptional profile and that this novel cell population is phenotypically and functionally distinct from previously described populations of naive and memory CD4(+) T cells. Naive-like T-bet-experienced cells are polarized to the T(H)1 lineage, predisposed to produce IFN-gamma 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.