Fig. 3: IL-7R^sup-hi naïve CD4 T cells are poised for a Th1 response.

a Graph showing significantly over-represented pathways for up-regulated genes in murine naïve CD4 T cell C1 cluster. The blue bar represents pathway significance (-log10 p.adjust), while the red line shows the count of up-regulated C1 genes involved in each pathway. Statistical significance was calculated using a one-sided hypergeometric test in ConsensusPathDB. b-c Cytokine receptor expression in IL-7R^sup-hi and IL-7R^low naïve CD4 T cells analyzed by (b) qPCR (n = 4) and (c) flow cytometry. d Representative CTV histogram of MOG- or OVA-activated 2D2 or OT-II IL-7R^sup-hi and IL-7R^low naïve CD4 T cells. e-f Representative dot plots of IL-7R^sup-hi and IL-7R^low naïve CD4 T cells stimulated with IL-18 and/or IL-12 (e) with anti-CD3/CD28 for 4 days or (f) with IL-7 for 5 days. g IFN-γ concentration in cultured media measured by ELISA (n = 8 for TCR, n = 7 for without TCR, with independent experiments conducted for each n). h–j Adoptive naive CD4 cell transfer to Rag-deficient mice. h Weekly weight normalized to day 0 (IL-7R^sup-hi n = 11; IL-7R^low n = 9; individual mice). i, j Cytokine production of transferred naïve CD4 T cells in (i) spleen and (j) mLN (IL-7R^sup-hi n = 11, IL-7R^low n = 9). k Two differentially accessible chromatin regions (DACR) potentially regulating Ifngr1 expression. The first two tracks show normalized accessibility signals for C1 and others from murine naive CD4 T cell scATAC-seq. Two DACRs are highlighted with arrows. Tracks 3-4 display gene locus positions and peaks from the scATAC-seq, while the fifth track shows inferred cis-regulatory interactions linking DACRs to Ifngr1. scATAC-seq data were reanalyzed from a previous study²⁷. l DACR2 center +-25bp region was zoomed in to show the TF motifs located in the middle of this region. The locations and the sequence logos of the Tbx21, Stat1, Stat4, and Eomes motifs were highlighted that are matched with the reference genome sequence in the reverse complementary manner. Motifs were annotated based on JASPAR database⁷⁴. Data presented as the mean ± S.D. Statistical significance of in 3 (b–j) was confirmed by the two-sided Mann-Whitney U-test (*p < 0.05, **p < 0.01) and two-way-ANOVA done in 3 h. Source data and exact statistics value are provided as a Source Data file.