Fig. 4: IL-7Rsup-hi naïve CD4 T cells exhibit cytolytic Th1 character, contributing to tumor rejection in response to IL-12/IL-18.
From: Th1-poised naive CD4 T cell subpopulation reflects anti-tumor immunity and autoimmune disease
a UMAP of scRNA-seq data from murine naïve CD4 T cells under different conditions including control (Naïve) and IL-7 treatment (Naïve_7) and IL-7 + 12 + 18 treatment (Naïve_7_12_18). Cells were colored by conditions. b UMAP of scRNA-seq colored by pseudotime inference using Monocle3. c UMAP of naïve CD4 T cells colored by the expression level of various marker genes (Tbs21, Ifng, Mki67, Gzmb) or gene sets (Naïve score, Th1 score). d Group of pseudotime dependently changed genes clustered by k-means clustering algorithm. X-axis and y-axis correspond to rank of cells ordered by pseudotime and z-score of expression level, respectively. e Dot plot showing the significance of pathway over-representation by the marker genes of each clusters. f Representative histogram of granzyme B expression. g The concentration of granzyme B in cultured media was measured by ELISA (n = 5 for TCR, n = 6 for without TCR, with independent experiments conducted for each n). h, i Tumor survival rate measured by CCK-8 in co-culture with B16F10 and naïve CD4 T cells cultured by (h) IL-7 (n = 4) or (i) IL-7/12/18 (n = 5) at indicated E:T ratio (E: effector, T: tumor). j Representative lung image and k the number of pleural tumor nodules in IL-12/18-activated OT-II IL-7Rsup-hi or IL-7Rlow naïve CD4 T cell injected B16F10 lung metastasis model (tumor only n = 7, IL-7Rsup-hi n = 7, IL-7Rlow n = 6). l Representative lung image and m the number of pleural tumor nodules in IL-12/18-activated WT or IFN-γ KO naïve CD4 T cell injected B16F10 lung metastasis model (tumor only n = 7, WT IL-7 n = 4, WT IL-7/12/18 n = 7, KO IL-7 n = 2, KO IL-7/12/18 n = 6). n Representative histogram of granzyme B and T-bet in WT or IFN-γ KO naïve CD4 T cells stimulated by cytokines indicated, analyzed by flow cytometry. DATA are presented as the mean ± S.D. Statistical significance of in 4 (g–m) was confirmed by the two-sided Mann-Whitney U-test (*p < 0.05, **p < 0.01, ***p < 0.001). Source data and exact statistics value are provided as a Source Data file.
