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

T-bet是CD4+辅助性T细胞1型（TH1）的谱系特异性转录因子。研究还发现，T-bet在TH17细胞、调节性T细胞（TREG）等其他CD4+ T细胞亚群中均有表达，并可调控这些亚群的功能特性。然而，目前学界对于T细胞分化过程中T-bet的具体表达时相与组织部位，以及其对T细胞功能的调控机制仍缺乏清晰认知。为解决这一科学问题，本研究借助荧光命运标记小鼠品系，追踪了表达T-bet的细胞的个体发育轨迹。本研究证实，T-bet表达于部分初始态CD4+ T细胞亚群，且这一全新细胞群体在表型与功能上均有别于传统初始态CD4+ T细胞；同时，该细胞群体也与此前已报道的记忆表型或干细胞样T细胞群体存在显著差异。经T-bet印记的初始态T细胞会向TH1谱系极化，在细胞激活时倾向于分泌干扰素γ（IFN-γ），且在体内外均难以被重极化至其他T细胞谱系。上述研究结果表明，谱系特异性转录因子可在T细胞激活前即促使初始态T细胞发生极化，这一过程会对后续的辅助性T细胞应答产生重要影响。整体实验设计：对从T-bet cre/+ Rosa26 YFP/+小鼠中纯化得到的初始态（CD62L+ CD44-）与记忆性（CD62L- CD44+）CD4+ T细胞中的YFP阳性与YFP阴性群体进行RNA测序比对分析。