Fig. 4: Identification of pathogen-specific T_FH phenotypes.

a–g, Bulk RNA-seq of sorted CD4⁺CD44⁺PD-1⁺CXCR5⁺FoxP3-RFP⁻IL-21–GFP⁺ T_FH, CD4⁺CD44⁺PD-1⁺CXCR5⁺FoxP3-RFP⁻IL-21–GFP⁻ T_FH cells from the draining lymph nodes of mice infected with the indicated pathogens (as in Fig. 1). MDS plot of CD4⁺CD44⁺PD-1⁺CXCR5⁺FoxP3-RFP⁻IL-21–GFP⁺ T_FH transcriptomes showing the separation of samples by infection type along dims 1 and 2 (a). Genes expressed differentially for T_FH (single infection vs. all other infections) and T_eff cells (single infection versus all other infections) (FDR < 0.05) (b). Orange, common pathogen-specific DE genes in both T_FH and T_eff cells; blue, pathogen-specific signatures unique to T_FH cells; red, pathogen-specific signatures unique to T_eff cells. Heatmaps of pathogen-specific T_FH signature genes (average row-based z score of normalized log₂ counts per million) for selected cytokine and cell surface receptor genes (c) and transcriptional regulator genes (d). Cytokine pathway genes from Mouse Genome Informatic (MGI) database gene sets indicated in colored circles. IFN (red), TNF (purple), IL-1 (pink), TGFβ (blue), IL-4 (green), IL-6 (yellow) and IL-17 (orange). Heatmap of pathogen-specific T_FH signature genes (average row-based z score of normalized log₂ counts per million) for selected signature-defining cytokines and chemokines for each infection (e) and lineage-defining transcription factors (f). GSEA of pathogen-specific signatures via MGI MSigDB ‘Hallmark’ gene sets for cytokine signaling and response (g). Bubble size represents the -log₁₀(FDR), and color indicates the NES. The data represent independent samples of 2–3 per cell type per infection. h, Analysis of draining lymph node CD4⁺CD44⁺CXCR5⁺PD-1⁺Ly6C⁻CD162⁻ T_FH cells from wild-type mice infected with indicated pathogens (as in Fig. 1) displaying gMFI of pathogen-specific T_FH signature marker (LCMV n = 7; T. muris n = 5; and C. rodentium n = 7 mice per group). Data show experiments of 5–7 mice per group and mean ± s.e.m. Statistical tests were one-way ANOVA of multiple comparisons and Pearson correlation with two-tailed P values. ****P < 0.0001 or otherwise indicated.

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