Top

Diagnostic Pathology

Published in:

Open Access 01-12-2012 | Research

The Intrahepatic Expression and Distribution of BTLA and its Ligand HVEM in patients with HBV-related acute-on-chronic liver failure

Authors: Huan Xu, Dayan Cao, Guoning Guo, Zhihua Ruan, Yuzhang Wu, Yongwen Chen

Published in: Diagnostic Pathology | Issue 1/2012

Abstract

Objective

It 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.

Methods

In 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.

Results

The 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.

Conclusions

These 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 slides

The virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/8080806838149123

Available only for authorised users

Stravitz RT, Kramer DJ: Management of acute liver failure. Nat Rev Gastroenterol Hepatol. 2009, 6: 542-553. 10.1038/nrgastro.2009.127.CrossRefPubMed

Liu Q, Liu Z, Wang T, et al.: Characteristics of acute and sub-acute liver failure in China: nomination, classification and interval. J Gastroen Hepatol. 2007, 22: 2101-2106. 10.1111/j.1440-1746.2006.04362.x.CrossRef

Liu M, Chan C, McGilvray I, et al.: Fulminant viral hepatitis: molecular and cellular basis, and clinical implications. Expert Rev Mol Med. 2001, 2001: 1-19.PubMed

Marsden PA, Ning Q, Fung L, et al.: The Fgl2/fibroleukin prothrombinase contributes to immunologically mediated thrombosis in experimental and human viral hepatitis. J Clin Invest. 2003, 112: 58-66.PubMedCentralCrossRefPubMed

Watanabe N, Gavrieli M, Sedy JR, et al.: BTLA is a lymphocyte inhibitory receptor with similarities to CTLA-4 and PD-1. Nat Immuno. 2003, 4: 670-679.CrossRef

Deppong C, Juehne TI, Hurchla M, et al.: Cutting edge: B and T lymphocyte attenuator and programmed death receptor-1 inhibitory receptors are required for termination of acute allergic airway inflammation. J Immunol. 2006, 176: 3909-3913.CrossRefPubMed

Oya Y, Watanabe N, Owada T, et al.: Development of autoimmune hepatitis-like disease and production of autoantibodies to nuclear antigens in mice lacking B and T lymphocyte attenuator. Arthritis Rheum. 2008, 58: 2498-2510. 10.1002/art.23674.PubMedCentralCrossRefPubMed

Tao R, Wang L, Han R, et al.: Differential effects of B and T lymphocyte attenuator and programmed death-1 on acceptance of partially versus fully MHC-mismatched cardiac allografts. J Immunol. 2005, 175: 5774-5782.CrossRefPubMed

Serriari NE, Gondois-Rey F, Guillaume Y, et al.: B and T lymphocyte attenuator is highly expressed on CMV-specific T cells during infection and regulates their function. J Immunol. 2010, 185: 3140-3148. 10.4049/jimmunol.0902487.CrossRefPubMed

10.

Sun Y, Brown NK, Ruddy MJ, et al.: B and T lymphocyte attenuator tempers early infection immunity. J Immunol. 2009, 183: 1946-1951. 10.4049/jimmunol.0801866.PubMedCentralCrossRefPubMed

11.

Sedy JR, Gavrieli M, Potter KG, et al.: B and T lymphocyte attenuator regulates T cell activation through interaction with herpesvirus entry mediator. Nat Immunol. 2005, 6: 90-98.CrossRefPubMed

12.

Gavrieli M, Watanabe N, Loftin SK, et al.: Characterization of phosphotyrosine binding motifs in the cytoplasmic domain of B and T lymphocyte attenuator required for association with protein tyrosine phosphatases SHP-1 and SHP-2. Biochem Biophys Res Commun. 2003, 312: 1236-1243. 10.1016/j.bbrc.2003.11.070.CrossRefPubMed

13.

Yang C, Chen Y, Guo G, et al.: Expression of B and T lymphocyte attenuator (BTLA) in macrophages contributes to the fulminant hepatitis caused by murine hepatitis virus strain-3. Gut. 2012, Jun 9. [Epub ahead of print]

14.

Cao D, Xu H, Guo G, et al.: Intrahepatic Expression of Programmed Death-1 and its Ligands in Patients with HBV-Related Acute-on-Chronic Liver Failure. Inflammation. 2012, Aug 16. [Epub ahead of print]

15.

Guo G, Cao D, Xu H, et al.: The characteristic expression of B7-H3 and B7-H4 in liver biopsies from patients with HBV-related acute-on-chronic liver failure. Pathology Int. 2012, 62: 665-674. 10.1111/j.1440-1827.2012.02856.x.CrossRef

16.

Murphy TL, Murphy KM: Slow down and survive: Enigmatic immunoregulation by BTLA and HVEM. Annu Rev Immunol. 2010, 28: 389-411. 10.1146/annurev-immunol-030409-101202.CrossRefPubMed

17.

Derré L, Rivals JP, Jandus C, et al.: BTLA mediates inhibition of human tumor-specific CD8+ T cells that can be partially reversed by vaccination. J Clin Invest. 2010, 120: 157-167. 10.1172/JCI40070.PubMedCentralCrossRefPubMed

18.

Pasero C, Speiser DE, Derré L, et al.: The HVEM network: new directions in targeting novel costimulatory/co-inhibitory molecules for cancer therapy. Curr Opin Pharmacol. 2012, 12: 478-485. 10.1016/j.coph.2012.03.001.CrossRefPubMed

19.

Nascimento C, Bottino A, Nogueira C, et al.: Analysis of morphological variables and arterialization in the differential diagnosis of hepatic nodules in explanted cirrhotic livers. Diagn Pathol. 2007, 2: 51-10.1186/1746-1596-2-51.PubMedCentralCrossRefPubMed

20.

Das P, Jain D, Das A: A retrospective autopsy study of histopathologic spectrum and etiologic trend of fulminant hepatic failure from north India. Diagn Pathol. 2007, 2: 27-10.1186/1746-1596-2-27.PubMedCentralCrossRefPubMed

21.

Dong H, Zhu G, Tamada K, et al.: B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat Med. 1999, 5: 1365-1369. 10.1038/70932.CrossRefPubMed

22.

Latchman Y, Wood CR, Chernova T, et al.: PD-L2 is a second ligand for PD-1 and inhibits T cell activation. Nat Immuno. 2001, 2: 261-268. 10.1038/85330.CrossRef

23.

Chapoval AI, Ni J, Lau JS, et al.: B7-H3: A costimulatory molecule for T cell activation and IFN-gamma production. Nat Immunol. 2001, 2: 269-274. 10.1038/85339.CrossRefPubMed

24.

Hashiguchi M, Kobori H, Ritprajak P, et al.: Triggering receptor expressed on myeloid cell-like transcript 2 (TLT-2) is a counterreceptor for B7-H3 and enhances T cell responses. Proc Natl Acad Sci USA. 2008, 105: 10495-10500. 10.1073/pnas.0802423105.PubMedCentralCrossRefPubMed

25.

Sica GL, Choi IH, Zhu G, et al.: B7-H4, a molecule of the B7 family, negatively regulates T cell immunity. Immunity. 2003, 18: 849-861. 10.1016/S1074-7613(03)00152-3.CrossRefPubMed

26.

Prasad DV, Richards S, Mai XM, et al.: B7S1, a novel B7 family member that negatively regulates T cell activation. Immunity. 2003, 18: 863-873. 10.1016/S1074-7613(03)00147-X.CrossRefPubMed

27.

Suh WK, Wang S, Duncan GS, et al.: Generation and characterization of B7-H4/B7S1/B7x-deficient mice. Mol Cell Biol. 2006, 26: 6403-6411. 10.1128/MCB.00755-06.PubMedCentralCrossRefPubMed

28.

Zhu G, Augustine MM, Azuma T, et al.: B7-H4-deficient mice display augmented neutrophil-mediated innate immunity. Blood. 2009, 113: 1759-1767. 10.1182/blood-2008-01-133223.PubMedCentralCrossRefPubMed

Title: The Intrahepatic Expression and Distribution of BTLA and its Ligand HVEM in patients with HBV-related acute-on-chronic liver failure
Authors: Huan Xu
Dayan Cao
Guoning Guo
Zhihua Ruan
Yuzhang Wu
Yongwen Chen
Publication date: 01-12-2012
Publisher: BioMed Central
Published in: Diagnostic Pathology / Issue 1/2012
Electronic ISSN: 1746-1596
DOI: https://doi.org/10.1186/1746-1596-7-142

2024 ASCO Annual Meeting

Springer Medicine

The Intrahepatic Expression and Distribution of BTLA and its Ligand HVEM in patients with HBV-related acute-on-chronic liver failure

Abstract

Objective

Methods

Results

Conclusions

Virtual slides

2024 ASCO Annual Meeting

Springer Medicine

Abstract

Objective

Methods

Results

Conclusions

Virtual slides

Please log in to get access to this content

Other articles of this Issue 1/2012

CD20-positive NK/T-cell lymphoma with indolent clinical course: report of case and review of literature

Immunohistochemistry profiles of breast ductal carcinoma: factor analysis of digital image analysis data

EGFR, CD10 and proliferation marker Ki67 expression in ameloblastoma: possible role in local recurrence

Primary Intravascular large B-cell lymphoma of lung: a report of one case and review

Association of COMT Val158Met polymorphism and breast cancer risk: an updated meta-analysis

Primary central nervous system plasmablastic lymphoma presenting in human immunodeficiency virus-negative but Epstein-Barr virus-positive patient: A case report