Increased CD86 but Not CD80 and PD-L1 Expression on Liver CD68(+) Cells during Chronic HBV Infection

BACKGROUND: The failure to establish potent anti-HBV T cell responses suggests the absence of an effective innate immune activation. Kupffer cells and liver-infiltrating monocytes/macrophages have an essential role in establishing anti-HBV responses. These cells express the costimulatory molecules CD80 and CD86. CD80 expression on antigen-presenting cells (APCs) induces Th1 cell differentiation, whereas CD86 expression drives the differentiation towards a Th2 profile. The relative expression of CD80, CD86 and PD-L1 on APCs, regulates T cell activation. Few studies investigated CD80 and CD86 expression on KCs and infiltrating monocytes/macrophages in HBV-infected liver and knowledge about the expression of PD-L1 on these cells is controversial. The expression of these molecules together in CD68(+) cells has not been explored in HBV-infected livers. METHODS: Double staining immunohistochemistry was applied to liver biopsies of HBV-infected and control donors to explore CD80, CD86 and PD-L1 expression in the lobular and portal areas. RESULTS: Chronic HBV infection was associated with increased CD68(+)CD86(+) cell count and percentage in the lobular areas, and no changes in the count and percentage of CD68(+)CD80(+) and CD68(+)PD-L1(+) cells, compared to the control group. While CD68(+)CD80(+) cell count in portal areas correlated with the fibrosis score, CD68(+)CD80(+) cell percentage in lobular areas correlated with the inflammation grade. CONCLUSION: The upregulation of CD86 but not CD80 and PD-L1 on CD68(+) cells in HBV-infected livers, suggests that these cells do not support the induction of potent Th1. Moreover, the expression of CD80 on CD68(+) cells correlates with liver inflammation and fibrosis.