Fig. 5: Pathogen-specific T_FH phenotypes are directed by distinct cytokine signaling pathways.

a–d, Analysis of draining lymph nodes from Tgfbr2-Lck^Cre and Lck^Cre control mice infected with influenza A virus in intact mice (a,c,d) and 50:50 bone marrow chimera mice (b). CXCR3⁺ T_FH1, CXCR3⁻CCR6⁻ T_FH2, and CCR6⁺ T_FH17 cells within CD4⁺CD44⁺CXCR5⁺PD-1⁺Ly6C⁻CD162⁻ T_FH cells are displayed as parts of the whole population (a,b). Frequency within T_FH population, and representative histograms of CXCR3 and CCR6 expression on T_FH cells (n = 9–10 mice per group) (a). The inner slice of the pie chart displays CXCR3⁺CCR6⁺ coexpression. Wild-type and Tgfbr2-Lck^Cre cells were identified by congenic marker expression (b). Frequency of CXCR3⁺ T_FH1, CXCR3⁻CCR6⁻ T_FH2, and CCR6⁺ T_FH17 cells and frequency of IFNγ⁺ T_FH1 cells within CD4⁺CD44⁺CXCR5⁺PD-1⁺Ly6C⁻CD162⁻ T_FH cells (n = 10 mice per group). The inner slice of the pie chart displays CXCR3⁺CCR6⁺ coexpression. IgG1 or IgG2c class switched B220⁺IgD^loCD95⁺ GC B cells and CD86⁻CXCR4⁺ dark zone (DZ) or CD86⁺CXCR4⁻ light zone (LZ) B cells on B220⁺IgD^loCD95⁺ GC B cells (n = 7–10 mice per group) (c). Serum IgG isotype concentration (d). e–h Draining lymph node analysis of Ifnar^−/− and Ifnar ^+/+ control mice infected with LCMV in intact mice (e,g,h) and 50:50 bone marrow chimera mice (f). CXCR3⁺ T_FH1, CXCR3⁻CCR6⁻ T_FH2, and CCR6⁺ T_FH17 cells within CD4⁺CD44⁺CXCR5⁺PD-1⁺Ly6C⁻CD162⁻ T_FH cells are displayed as parts of the whole population (e,f). Frequency within T_FH population, and representative histograms of CXCR3 and CCR6 expression on T_FH cells (n = 7 mice per group) (e). The inner slice of the pie chart displays CXCR3⁺CCR6⁺ coexpression. Wild-type and Ifnar^−/− cells were identified by congenic marker expression (f). Frequency of CXCR3⁺ T_FH1, CXCR3⁻CCR6⁻ T_FH2, and CCR6⁺ T_FH17 cells and frequency of IFNγ⁺ T_FH1 cells within CD4⁺CD44⁺CXCR5⁺PD-1⁺Ly6C⁻CD162⁻ T_FH cells (n = 8 mice per group). The inner slice of the pie chart displays CXCR3⁺CCR6⁺ coexpression. IgG1 or IgG2c class switched B220⁺IgD^loCD95⁺ GC B cells and CD86⁻CXCR4⁺ DZ or CD86⁺CXCR4⁻ LZ B cells from B220⁺IgD^loCD95⁺ GC B cells (n = 7 mice per group) (g). Serum IgG isotype concentration (h). The data are from 7–10 mice per group and are presented as the mean ± s.e.m. Statistical tests were a two-tailed unpaired Student’s t-test for the intact system and a two-tailed paired Student’s t-test for the bone marrow chimera model. ****P < 0.0001 or otherwise indicated.

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