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 5
VZV-mediated regulation of PD-L1, PD-L2 and PD-1 expression in human monocytes, B cells, NK cells and NKT cells.
Human PBMCs 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 and VZV gE expression using flow cytometry. (A) Flow cytometry gating strategy for uninfected (UI), VZV gE-negative bystander (Bys) and VZV gE+ (V+) immune cell populations. (B) Representative flow cytometry plots of PD-L1, PD-L2 and PD-1 MFI expression levels in monocytes (Mono), NK cells, NKT cells and B cells. Black histograms = FMO control, grey histograms = UI, blue histograms = Bys and red histograms = V+ cells. (C-E) Summary of fold change in MFI in PD-L1 (C), PD-L2 (D) and PD-1 (E) expression levels in: Bys/UI (blue), V+/UI (red) and V+/Bys (red with black stripes) with respect to all immune cell populations analyzed. Results are representative of eight independent experiments with PBMCs from eight healthy individuals. Bar graphs represent average fold-change in MFI ± SEM. *P<0.05, **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.