A Potential Inhibitory Profile of Liver CD68+ Cells during HCV Infection as Observed by an Increased CD80 and PD-L1 but Not CD86 Expression

Aim The lack of potent innate immune responses during HCV infection might lead to a delay in initiating adaptive immune responses. Kupffer cells (KCs) and liver-infiltrating monocytes/macrophages (CD68 + cells) are essential to establish effective anti-HCV responses. They express co-stimulatory molecules, CD80 and CD86. CD86 upregulation induces activator responses that are then potentially regulated by CD80. The relative levels of expression of CD80, CD86 and the inhibitory molecule, PD-L1, on CD68 + cells modulate T cell activation. A few studies have explored CD80 and PD-L1 expression on KCs and infiltrating monocytes/macrophages in HCV-infected livers, and none investigated CD86 expression in these cells. These studies have identified these cells based on morphology only. We investigated the stimulatory/inhibitory profile of CD68 + cells in HCV-infected livers based on the balance of CD80, CD86 and PD-L1 expression. Methods CD80, CD86 and PD-L1 expression by CD68 + cells in the lobular and portal areas of the liver of chronic HCV-infected (n = 16) and control (n = 14) individuals was investigated using double staining immunohistochemistry. Results The count of CD68 + KCs in the lobular areas of the HCV-infected livers was lower than that in the control ( p = 0.041). The frequencies of CD68 + CD80 + cells and CD68 + PD-L1 + cells in both lobular and total areas of the liver were higher in HCV-infected patients compared with those in the control group ( p = 0.001, 0.031 and 0.007 respectively). Moreover, in the lobular areas of the HCV-infected livers, the frequency of CD68 + CD80 + cells was higher than that of CD68 + CD86 + and CD68 + PD-L1 + cells. In addition, the frequencies of CD68 + CD80 + and CD68 + CD86 + cells were higher in the lobular areas than the portal areas. Conclusions Our results show that CD68 + cells have an inhibitory profile in the HCV-infected livers. This might help explain the delayed T cell response and viral persistence during HCV infection.