Varicella zoster virus productively infects human peripheral blood mononuclear cells to modulate expression of immunoinhibitory proteins and blocking PD-L1 enhances virus-specific CD8+ T cell effector function
Fig 6
VZV-mediated regulation of PD-1, PD-L1, PD-L2, CTLA-4, LAG-3 and TIM-3 expression in human CD4+ and CD8+ T cells.
Human PBMCs from Fig 4 were co-cultured with uninfected- or VZV-infected HFLs for 48 h as described in Fig 1 then harvested and analyzed for PD-1, PD-L1, PD-L2, CTLA-4, LAG-3, TIM-3 and VZV gE expression using flow cytometry. (A) Representative flow cytometry plots of PD-1, PD-L1, PD-L2, CTLA-4, LAG-3 and TIM-3 MFI expression levels in CD4+ and CD8+ T cells. Black histograms = FMO control, grey histograms = UI, blue histograms = Bys and red histograms = V+ cells. (B) Summary of fold change in MFI in PD-1, PD-L1, PD-L2, CTLA-4, LAG-3 and TIM-3 expression levels in: Bys/UI (blue), V+/UI (red) and V+/Bys (red with black stripes) with respect to CD4+ and CD8+ T cells. Results are representative of eight independent experiments with PBMCs from eight healthy individuals that are from the same experiments shown in Fig 4. Bar graphs represent average fold-change in MFI ± SEM. **P<0.01, ***P<0.001, ****P<0.0001. Statistical significance was determined using RM one-way ANOVA with the Greenhouse-Geisser correction and Tukey posttest.