Abstract
ObjectiveIt has been demonstrated that signals from the inhibitory receptor B and T lymphocyte attenuator (BTLA) are involved in regulating the pathogenesis of infectious diseases. However, the expression and anatomical distribution of BTLA and its ligand, the herpes virus entry mediator (HVEM), have not yet been determined in cases of HBV-related acute-on-chronic liver failure (HBV-ACLF) patients.MethodsIn this study, the expression of BTLA and HVEM in liver tissues from HBV-ACLF, chronic hepatitis B (CHB) patients and healthy individuals was analyzed by immunohistochemistry.ResultsThe results of this analysis demonstrated that both molecules were observed in the HBV-ACLF samples and that their expression was chiefly in the infiltrating inflammatory cells and the damaged bile ducts. However, they were absent in liver sections from CHB patients and healthy controls. Immunofluorescence double-staining indicated that BTLA was found on CK-18+ epithelial cells, CD31+ endothelial cells, CD68+ macrophages, CD56+ NK cells, CD16+ monocytes, CD3+ , CD8+ T cells, and Foxp3+ regulatory T cells (Treg). By contrast, HVEM expression was restricted to CK18+ epithelial cells and CD68+ macrophages. Moreover, the expression of several members of the B7 superfamily, including PD-L1, PD-L2, B7-H3 and B7-H4, was also detected in these liver tissues, and these proteins were co-expressed with HVEM. Interestingly, the expression of fibrinogen-like protein 2 (FGL2), a virus-induced procoagulant molecule, was also found in liver sections from HBV-ACLF, this molecule also co-expresses with BTLA and HVEM.ConclusionsThese results suggest that BTLA-HVEM signaling is likely to affect the pathogenesis of HBV-ACLF, a clear understanding of the functional roles of these proteins should further elucidate the disease process.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/8080806838149123
Highlights
Hepatitis B virus (HBV) infection causes a spectrum of diseases, such as chronic hepatitis B (CHB), liver cirrhosis, primary hepatocellular carcinoma, and acute-on-chronic liver failure (ACLF) [1]
The pathologic characteristics of liver tissue from HBV-ACLF To address the relevance of B and T lymphocyte attenuator (BTLA) and Herpes virus entry mediator (HVEM) expression in human viral hepatitis, four liver biopsies from patients with biochemical, histological, and clinical evidence of HBV-ACLF, sixteen cases of CHB patients and five cases of healthy individuals were collected in this study
The expression and anatomical distribution of BTLA in sections from HBV-ACLF The expression of BTLA in liver samples from HBVACLF patients, CHB patients and healthy individuals was detected by immunohistochemistry
Summary
Hepatitis B virus (HBV) infection causes a spectrum of diseases, such as chronic hepatitis B (CHB), liver cirrhosis, primary hepatocellular carcinoma, and acute-on-chronic liver failure (ACLF) [1]. For instance, it has been found that an interruption of BTLA signaling causes the augmentation of the virus-specific cytotoxic lymphocyte (CTL) response, promoting the early clearance of both Listeria bacteria and CMV infection [9,10]. These studies generally indicate that BTLA appears to be a negative regulator. The cross-linking of BTLA with HVEM results in the phosphorylation of the tyrosines on BTLA and the recruitment of phosphatases, including SHP-1 and SHP-2, to the ITIM motif in the cytoplasmic region of BTLA, this response reduces TCR signaling and eventually diminishes T cell activation [12]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
