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

Abstract

AimThe 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.MethodsCD80, 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.ResultsThe 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.ConclusionsOur 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.

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

“…The control group also included biopsies of unaffected areas for secondary hepatic malignancy (carcinoma). This control group was also used in a study, which was done in parallel, to investigate CD80, CD86 and PD-L1 expression in liver CD68 + cells during chronic HCV infection [ 27 ]. Since the experimental procedure consisted of staining biopsies that were already done and stored in the bank of the Pathology Department, and did not implicate any special sample (biopsy) collection (article 32 of the Declaration of Helsinki), patients consent was impracticable to obtain.…”

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.…”

The Reduction in CD8+PD1+ T Cells in Liver Histological Tissue is Related to Pegylated IFN-α Therapy Outcomes in Chronic Hepatitis B Patients

“…18,24 In liver tissue, CD68 + mononuclear cells were regarded as KCs and liver-infiltrating monocytes/macrophages. 16,17 Reports showed HBV particles and HBsAg induce IL-1b, IL-6, CXCL8, and TNF production by human CD68 + cell-enriched non-parenchymal cells via NF-κB activation and subsequently inhibit HBV replication in primary hepatocytes. 25 Our study showed that CD68 + mononuclear cells in the FIRENR group were higher than in the FIENR group at baseline, and CD68 + mononuclear cells significantly increased in the FIER group after 6 months of PEG-IFN-α therapy.…”

“…In liver tissue, CD68 + mononuclear cells were regarded as Kupffer cells (KCs) and liver-infiltrating monocytes/macrophages. 16,17 Studies showed that these cells could induce pro-inflammatory response inhibition of viral replication, which is important for the inhibition of viral replication. 18 KC virus interactions can also inhibit the development of effective viral immunity, facilitate viral persistence, or promote liver damage.…”