A population of CD4+ T cells with a naïve phenotype stably polarized to the Th1 lineage

T-bet is the lineage-specifying transcription factor for CD4+ T helper type 1 (TH1) cells. T-bet has also been found in other CD4+ T cell subsets, including TH17 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 the T cell 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 naïve CD4+ T cells and that this novel cell population is phenotypically and functionally distinct from conventional naïve CD4+ T cells. These cells are also distinct from previously described populations of memory phenotype or stem cell-like T cells. Naïve T-bet-experienced cells are polarised to the TH1 lineage, predisposed to produce IFN upon cell activation, and resist repolarisation to other lineages in vitro and in vivo. These results demonstrate that lineage-specifying factors can function to polarise naïve T cells prior to T cell activation and that this has an impact on the subsequent T helper response. RNA sequencing data comparing YFP+ and YFP- Naïve (CD62L+ CD44-) and Memory (CD62L-CD44+) CD4+ T cells purified from T-bet cre/+ Rosa26 YFP/+ mice.