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

Abstract

BackgroundThe 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.MethodsDouble 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.ResultsChronic 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.ConclusionThe 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.

<p>Functional aspects, phenotypic heterogeneity, and tissue immune response of macrophages in infectious diseases</p>

“…Thorough elucidation of these groups of markers, or panels, has revealed that these phenotypes are distinguished by expression differences in chemokines, chemokine receptors, enzymes, costimulatory molecules, Toll receptors, cytokines, and cytokine receptors. [39][40][41][42][43] M1 macrophages express inducible nitric oxide synthase (iNOS), the primary marker that confirms the response of these cells in a specific disease (Table 1). [44][45][46] However, a surface marker that defines the identity of M1 macrophages has not yet been identified.…”

Liver macrophages: Friend or foe during hepatitis B infection?

“…At the peak of viraemia, during the inhibition of lymphocyte activation, a peak of IL‐10 was observed in the serum. Moreover, in chronically infected HBV patients an increase of CD68 + CD86 + MΦ was observed, promoting a specific Th2 response, thus promoting of phagocytic‐independent inflammation . Lastly, Nebbia et al.…”

The Reduction in CD8+PD-1+ T Cells in Liver Histological Tissue is Related to Pegylated IFN-α Therapy Outcomes in Chronic Hepatitis B Patients

“…16,22 In liver tissue, CD68 + mononuclear cells were regarded as KCs and liver-in ltrating monocytes/macrophages. 14,15 NF-κB activation in CD68 + cell-enriched cell by HBV particles or HBsAg will induce the production of IL-1b, IL-6, CXCL8, and TNF, which can inhibit virus replication in primary hepatocytes. 23 Our study showed that CD68 + mononuclear cells signi cantly increased in the FIER group after treating with PEG-IFN-α for 6 months.…”