Extended Data Fig. 4: CD4+ T cells prevent and revert CD8+ T cell dysfunction.

(a) MFIs of indicated markers (Fig. 2I) on Env28 T cells or control CD8+ T cells. (b) MFIs of indicated markers (of Fig. 2I) on Env28 T cells in indicated conditions or control CD8+ T cells. (c) Experimental design: HBV-sp CD8+ TN cells were transferred in HBV Tg mice transferred 7 days later with Env126 CD4+ TEFF. Single transfer of CD8+ T cells (CD8) and untreated HBV Tg mice (PBS) were used as controls. (d) sALT at indicated time points post CD4+ TEFF transfer. (e) IHL in indicated groups at day 5 post CD4+ TEFF transfer. (f) Frequency and numbers of hepatic HBV-specific CD8+ T cells at day 5 post Env126 CD4+ TEFF transfer. (g) Numbers of IFN-γ producing hepatic HBV-specific CD8+ T cells t day 5 post Env126 CD4+ TEFF transfer. (h) Env28 T cells frequency in spleen and liver draining lymph nodes at day 5 post cell transfer (refers to Fig. 2A). (i) Experimental design: Env126 CD4+ TEFF were transferred in 1:1 ratio (2,5×105:2,5×105 or 5×104: 5×104) with naïve HBV-specific CD8+ T cells in HBV Tg mice (Co-T). Single transfer of CD8+ T cells (CD8) and untreated HBV Tg mice (PBS) were used as controls. (j) Hepatic HBV-specific CD8+ T cells numbers at day 5 post transfer. (k) Numbers of IFNγ producing hepatic HBV-specific CD8+ T cells at day 5 post transfer. (l) Grzm-B producing hepatic HBV-specific CD8+ T cells numbers at day 5 post transfer. (m) Representative flow cytometry plots showing the frequency of Sca-1+ HBV-specific CD8+ T cells at day 5 post transfer. (n) Sca-1 MFI on HBV-specific CD8+ T cells or control CD8+ T cells. (a-b, h) n = 3 (PBS), 4 (Env28), 5 (Co-T). Data are representative of at least 10 independent experiments. (c-g) n = 3 (PBS), 4 (CD8), 6 (Co-T). (j-n) n = 2 (PBS), 2 (CD8 5×104), 4 (Co-T 5×104), 3 (CD8 2,5×105), 3 (Co-T 2,5×105). Data are representative of at least 3 independent experiments. Data are expressed as mean ± SEM. P values were calculated with two-way ANOVA with Bonferroni post-test. * P<0.05, ** P<0.01, *** P<0.001.