HBcAg induces PD-1 upregulation on CD4+T cells through activation of JNK, ERK and PI3K/AKT pathways in chronic hepatitis-B-infected patients

Laboratory Investigation

Volumn 92, Issue 2, 2012, Pages 295-304

  Li, Man ^a   Sun, Xue Hua ^a   Zhu, Xiao Jun ^a   Jin, Shu Gen ^a   Zeng, Zhen Jun ^a   Zhou, Zhen Hua ^a   Yu, Zhuo ^a   Gao, Yue Qiu ^a  

^a SHANGHAI UNIVERSITY OF TRADITIONAL CHINESE MEDICINE   (China)

Author keywords

chronic HBV infection; HBcAg; PD 1

Indexed keywords

ALANINE AMINOTRANSFERASE; HEPATITIS B CORE ANTIGEN; MITOGEN ACTIVATED PROTEIN KINASE; PHOSPHATIDYLINOSITOL 3 KINASE; PROGRAMMED DEATH 1 RECEPTOR; PROTEIN KINASE B; STRESS ACTIVATED PROTEIN KINASE; VIRUS DNA;

ADULT; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ARTICLE; CD4+ T LYMPHOCYTE; CHRONIC HEPATITIS; CORRELATION ANALYSIS; ENZYME INDUCTION; ENZYME INHIBITION; FEMALE; HEPATITIS B; HUMAN; IMMUNOLOGICAL TOLERANCE; MAJOR CLINICAL STUDY; MALE; PERIPHERAL BLOOD MONONUCLEAR CELL; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN INDUCTION; SIGNAL TRANSDUCTION; VIRAL CLEARANCE; VIRUS CARRIER;

EID: 84863011585     PISSN: 00236837     EISSN: 15300307     Source Type: Journal    
DOI: 10.1038/labinvest.2011.157     Document Type: Article

References (56)

1. Ganczak M, Szych Z, Korzen M. Preoperative vaccination for HBV at Polish hospitals as a possible public health tool to limit the spread of the epidemic: a cross-sectional study. Vaccine 2009;27:3969-3974.
2. Hong WD, Zhu QH, Huang ZM, et al. Predictors of esophageal varices in patients with HBV-related cirrhosis: a retrospective study. BMC Gastroenterol 2009;9:11.
3. Lee WM. Hepatitis B virus infection. N Engl J Med 1997;337:1733-1745. (Pubitemid 27527771)
4. McMahon BJ. Epidemiology and natural history of hepatitis B. Semin Liver Dis 2005;25(Suppl 1):3-8. (Pubitemid 41254588)
5. Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology 2007;45: 507-539. (Pubitemid 46374607)
6. Pan CQ, Zhang JX. Natural history and clinical consequences of hepatitis B virus infection. Int J Med Sci 2005;2:36-40. (Pubitemid 40944951)
7. Shi YH, Shi CH. Molecular characteristics and stages of chronic hepatitis B virus infection. World J Gastroenterol 2009;15:3099-3105.
8. Agata Y, Kawasaki A, Nishimura H, et al. Expression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytes. Int Immunol 1996;8:765-772. (Pubitemid 26148299)
9. Ishida Y, Agata Y, Shibahara K, et al. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J 1992;11:3887-3895.
10. Hatachi S, Iwai Y, Kawano S, et al. CD4+ PD-1+ T cells accumulate as unique anergic cells in rheumatoid arthritis synovial fluid. J Rheumatol 2003;30:1410-1419. (Pubitemid 36835433)
11. Liang SC, Latchman YE, Buhlmann JE, et al. Regulation of PD-1, PD-L1, and PD-L2 expression during normal and autoimmune responses. Eur J Immunol 2003;33:2706-2716. (Pubitemid 37337136)
12. Zhu B, Guleria I, Khosroshahi A, et al. Differential role of programmed death-ligand 1 [corrected] and programmed death-ligand 2 [corrected] in regulating the susceptibility and chronic progression of experimental autoimmune encephalomyelitis. J Immunol 2006;176: 3480-3489. (Pubitemid 43363995)
13. Day CL, Kaufmann DE, Kiepiela P, et al. PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression. Nature 2006;443:350-354. (Pubitemid 44435155)
14. Petrovas C, Casazza JP, Brenchley JM, et al. PD-1 is a regulator of virusspecific CD8+ T cell survival in HIV infection. J Exp Med 2006;203: 2281-2292. (Pubitemid 44498363)
15. Trautmann L, Janbazian L, Chomont N, et al. Upregulation of PD-1 expression on HIV-specific CD8+ T cells leads to reversible immune dysfunction. Nat Med 2006;12:1198-1202. (Pubitemid 44527357)
16. Penna A, Pilli M, Zerbini A, et al. Dysfunction and functional restoration of HCV-specific CD8 responses in chronic hepatitis C virus infection. Hepatology 2007;45:588-601. (Pubitemid 46450610)
17. Urbani S, Amadei B, Tola D, et al. PD-1 expression in acute hepatitis C virus (HCV) infection is associated with HCV-specific CD8 exhaustion. J Virol 2006;80:11398-11403. (Pubitemid 44706581)
18. Boni C, Fisicaro P, Valdatta C, et al. Characterization of hepatitis B virus (HBV)-specific T-cell dysfunction in chronic HBV infection. J Virol 2007;81:4215-4225. (Pubitemid 46586915)
19. Chen L, Zhang Z, Chen W, et al. B7-H1 upregulation on myeloid dendritic cells significantly suppresses T cell immune function in patients with chronic hepatitis B. J Immunol 2007;178:6634-6641. (Pubitemid 46717448)
20. Peng G, Li S, Wu W, et al. PD-1 upregulation is associated with HBVspecific T cell dysfunction in chronic hepatitis B patients. Mol Immunol 2008;45:963-970. (Pubitemid 350019503)
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.
22. Nishimura H, Honjo T. PD-1: an inhibitory immunoreceptor involved in peripheral tolerance. Trends Immunol 2001;22:265-268. (Pubitemid 32667515)
23. Probst HC, McCoy K, Okazaki T, et al. Resting dendritic cells induce peripheral CD8+ T cell tolerance through PD-1 and CTLA-4. Nat Immunol 2005;6:280-286. (Pubitemid 41724765)
24. Okazaki T, Honjo T. The PD-1-PD-L pathway in immunological tolerance. Trends Immunol 2006;27:195-201.
25. Hirano F, Kaneko K, Tamura H, et al. Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity. Cancer Res 2005;65:1089-1096. (Pubitemid 40216472)
26. Iwai Y, Terawaki S, Honjo T. PD-1 blockade inhibits hematogenous spread of poorly immunogenic tumor cells by enhanced recruitment of effector T cells. Int Immunol 2005;17:133-144. (Pubitemid 40246578)
27. Iwai Y, Terawaki S, Ikegawa M, et al. PD-1 inhibits antiviral immunity at the effector phase in the liver. J Exp Med 2003;198:39-50. (Pubitemid 36870184)
28. Maier H, Isogawa M, Freeman GJ, et al. PD-1:PD-L1 interactions contribute to the functional suppression of virus-specific CD8+ T lymphocytes in the liver. J Immunol 2007;178:2714-2720. (Pubitemid 46333147)
29. Hsu PN, Yang TC, Kao JT, et al. Increased PD-1 and decreased CD28 expression in chronic hepatitis B patients with advanced hepatocellular carcinoma. Liver Int 2010;30:1379-1386.
30. Zhang G, Liu Z, Duan S, et al. Association of polymorphisms of programmed cell death-1 gene with chronic hepatitis B virus infection. Hum Immunol 2010;71:1209-1213.
31. Kimura T, Rokuhara A, Matsumoto A, et al. New enzyme immunoassay for detection of hepatitis B virus core antigen (HBcAg) and relation between levels of HBcAg and HBV DNA. J Clin Microbiol 2003;41: 1901-1906. (Pubitemid 36576510)
32. Cao T, Meuleman P, Desombere I, et al. In vivo inhibition of antihepatitis B virus core antigen (HBcAg) immunoglobulin G production by HBcAg-specific CD4(+) Th1-type T-cell clones in a hu-PBL-NOD/SCID mouse model. J Virol 2001;75:11449-11456. (Pubitemid 33063236)
33. Miura Y, Thoburn CJ, Bright EC, et al. Association of Foxp3 regulatory gene expression with graft-versus-host disease. Blood 2004;104: 2187-2193. (Pubitemid 39297878)
34. Dure M, Macian F. IL-2 signaling prevents T cell anergy by inhibiting the expression of anergy-inducing genes. Mol Immunol 2009;46: 999-1006.
35. Andrade RM, Lima PG, Filho RG, et al. Interleukin-10-secreting CD4 cells from aged patients with AIDS decrease in-vitro HIV replication and tumour necrosis factor alpha production. AIDS 2007;21:1763-1770. (Pubitemid 47237564)
36. Muhlbauer M, Fleck M, Schutz C, et al. PD-L1 is induced in hepatocytes by viral infection and by interferon-alpha and -gamma and mediates T cell apoptosis. J Hepatol 2006;45:520-528. (Pubitemid 44307379)
37. Bowen DG, Shoukry NH, Grakoui A, et al. Variable patterns of programmed death-1 expression on fully functional memory T cells after spontaneous resolution of hepatitis C virus infection. J Virol 2008;82:5109-5114. (Pubitemid 351657073)
38. Zhang Z, Zhang JY, Wherry EJ, et al. Dynamic programmed death 1 expression by virus-specific CD8 T cells correlates with the outcome of acute hepatitis B. Gastroenterology 2008;134:1938-1949; 1949 e1931-1933.
39. Xie Z, Chen Y, Zhao S, et al. Intrahepatic PD-1/PD-L1 upregulation closely correlates with inflammation and virus replication in patients with chronic HBV infection. Immunol Invest 2009;38:624-638.
40. Nan XP, Zhang Y, Yu HT, et al. Circulating CD4+CD25high regulatory T cells and expression of PD-1 and BTLA on CD4+ T cells in patients with chronic hepatitis B virus infection. Viral Immunol 2010;23:63-70.
41. Muthumani K, Choo AY, Shedlock DJ, et al. Human immunodeficiency virus type 1 Nef induces programmed death 1 expression through a p38 mitogen-activated protein kinase-dependent mechanism. J Virol 2008;82:11536-11544.
42. Parry RV, Chemnitz JM, Frauwirth KA, et al. CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms. Mol Cell Biol 2005;25:9543-9553. (Pubitemid 41507854)
43. Chambers CA, Kuhns MS, Allison JP. Cytotoxic T lymphocyte antigen-4 (CTLA-4) regulates primary and secondary peptide-specific CD4(+) T cell responses. Proc Natl Acad Sci USA 1999;96:8603-8608. (Pubitemid 29354838)
44. Chambers CA, Sullivan TJ, Truong T, et al. Secondary but not primary T cell responses are enhanced in CTLA-4-deficient CD8+ T cells. Eur J Immunol 1998;28:3137-3143. (Pubitemid 28470259)
45. Bachmann MF, Waterhouse P, Speiser DE, et al. Normal responsiveness of CTLA-4-deficient anti-viral cytotoxic T cells. J Immunol 1998; 160:95-100. (Pubitemid 28116719)
46. Whitmire JK, Slifka MK, Grewal IS, et al. CD40 ligand-deficient mice generate a normal primary cytotoxic T-lymphocyte response but a defective humoral response to a viral infection. J Virol 1996;70: 8375-8381. (Pubitemid 26378413)
47. Coles MC, McMahon CW, Takizawa H, et al. Memory CD8 T lymphocytes express inhibitory MHC-specific Ly49 receptors. Eur J Immunol 2000;30:236-244. (Pubitemid 30011785)
48. Zhang JY, Zhang Z, Wang X, et al. PD-1 upregulation is correlated with HIV-specific memory CD8+ T-cell exhaustion in typical progressors but not in long-term nonprogressors. Blood 2007;109:4671-4678. (Pubitemid 46827757)
49. Golden-Mason L, Palmer B, Klarquist J, et al. Upregulation of PD-1 expression on circulating and intrahepatic hepatitis C virus-specific CD8+ T cells associated with reversible immune dysfunction. J Virol 2007;81:9249-9258. (Pubitemid 47311467)
50. Konkel JE, Frommer F, Leech MD, et al. PD-1 signalling in CD4(+) T cells restrains their clonal expansion to an immunogenic stimulus, but is not critically required for peptide-induced tolerance. Immunology 2010;130:92-102.
51. Iloeje UH, Yang HI, Su J, et al. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology 2006;130: 678-686. (Pubitemid 43374518)
52. McMahon BJ. The natural history of chronic hepatitis B virus infection. Hepatology 2009;49(5 Suppl):S45-S55.
53. Liang XS, Zhou Y, Li CZ, et al. Natural course of chronic hepatitis B is characterized by changing patterns of programmed death type-1 of CD8-positive T cells. World J Gastroenterol 2010;16:618-624.
54. Benn J, Su F, Doria M, et al. Hepatitis B virus HBx protein induces transcription factor AP-1 by activation of extracellular signal-regulated and c-Jun N-terminal mitogen-activated protein kinases. J Virol 1996;70:4978-4985. (Pubitemid 26240667)
55. Erhardt A, Hassan M, Heintges T, et al. Hepatitis C virus core protein induces cell proliferation and activates ERK, JNK, and p38 MAP kinases together with the MAP kinase phosphatase MKP-1 in a HepG2 Tet-Off cell line. Virology 2002;292:272-284. (Pubitemid 34920547)
56. Yamamoto R, Nishikori M, Tashima M, et al. B7-H1 expression is regulated by MEK/ERK signaling pathway in anaplastic large cell lymphoma and Hodgkin lymphoma. Cancer Sci 2009;100:2093-2100.