الملخص الإنجليزي
Antigen presenting cells (APCs) play a major role in the quality of the antiviral T cell responses by expressing co-stimulatory (CD80 and CD86) and co inhibitory (PD-L1) molecules. To date, few studies have analyzed the role of Kupffer cells (KCs), the most potent APCs in the liver, in HBV and HCV infections, and these studies identified KCs based only on the morphology. Moreover, Midkine (MK) isa heparin binding growth factorthought to be involved in liver regeneration. Aims: To investigate: (1) The expression of CD80, CD86, PD-LI on KCs of chronic HBV- and HCV-infected patients in comparison with healthy individuals. (2) Correlation between the expression of CD80, CD86, PD-L1 on KCs with the viral load, liver enzymes (ALT, AST, ALP), inflammation grade and fibrosis stage. (3) The production of MK by macrophages and monocytes-derived dendritic cells (MDDCs). Methods: Specimens of liver tissue of HBV-, HCV-infected patients (n=16 of each) and healthy individuals (n=14). Combinations of anti-CD68 and anti-CD80, anti CD86 or anti-PD-L1 were used to identify the stimulated KCs by immunohistochemistry. In addition, blood samples of 3 healthy individuals were collected to assess the production of MK. MK mRNA was quantified using quantitative RT-PCR and ELISA was used to quantify the MK protein. Results: CD80*KCs and PD-L1*KÇs were enriched within the liver of patients with chronic HCV while CD86+KCs are enriched within the liver of patients with chronic HBV. (2) Increased CD86 KCs in the portal area with the increase of HCV viral load while increased CD80+KCs with the fibrosis and inflammation grade in HBV infection. (3) No correlations were between the investigated molecules and liver enzymes in HBV-or HCV-infected patients. (4)The presence of MK mRNA and protein was detected in both macrophages and MDDCs. Conclusion: These findings indicate the importance of costimulatory and coinhibitory molecules expressed by KCs in the pathogenesis of HBV and HCV and suggest a potential role for macrophages and DCs expressing MK in the regeneration of hepatocytes. This might provide clues for new vaccination and therapeutic strategies targeting the immune response during HBV or HCV infections
