A population of CD4+ T cells with a naive phenotype stably polarized to the TH1 lineage

Abstract

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 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 CD4+ T cells with naive cell surface markers and that this novel cell population is phenotypically and functionally distinct from conventional naive CD4+ T cells. These cells are also distinct from previously described populations of memory phenotype and stem cell-like T cells. Naive-like T-bet-experienced cells are polarised to the TH1 lineage, predisposed to produce IFN{gamma} 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 T cells in the absence of canonical markers of T cell activation and that this has an impact on the subsequent T helper response.