Figure 6.
TRAIL-R2 expression is a feature of CD8+ T cells encountering antigen in the HBV-infected liver. (A) Representative gating strategy identifying intrahepatic TRAIL-R2+ high (red), TRAIL-R2+ low (black), and TRAIL-R2 negative (gray) CD8+ T cells from a CHB patient. Histograms and bars depict the proportions of CD38 (n = 4), Annexin V (n = 3), PD1 (n = 6), and CD57 (n = 8) expressed by each subset directly ex vivo. (B) The maturation status of intrahepatic TRAIL-R2+ high (red), TRAIL-R2+ low (black), and TRAIL-R2 negative (gray) CD8+ T cells were analyzed by co-staining for CD27 and CD45RA. Representative FACS plot and summary bars of frequencies of expression of TRAIL-R2+ high (red), TRAIL-R2+ low (black), and TRAIL-R2 negative (gray) CD8+ T cells with naive, central memory (CM), effector memory (EM) and revertant (EMRA) phenotypes from n = 4 CHB patients. (C) Summary bar graphs comparing expression of TRAIL-R2 on global intrahepatic CD8+ T cells, CMV-specific and HBV-specific CD8+ T cells. Virus-specific CD8+ T cells were identified directly ex vivo by multimer staining in (n = 5) HLA-A2+ CHB patients with available liver biopsies. (D) Representative examples of the gating strategy from a control patient with no evidence of viral hepatitis (control liver) and a CHB patient (HBV liver) showing expression of TRAIL-R2 on intrahepatic global CD8+ T cells and virus-specific CD8+ T cells identified via IFN-γ staining after overnight stimulation with CMV peptide and HBV overlapping peptides (OLP), respectively. Summary bar graphs comparing expression of TRAIL-R2 on CMV-specific CD8+ T cells from control livers (n = 5) versus CMV and HBV-specific CD8+ T cells from (n = 5) CHB patients. Bars represent the mean ± SEM. *, P < 0.05.