CD8(+) T Cells Mediate Viral Clearance and Disease Pathogenesis During Acute Hepatitis B Virus Infection

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2002 Dec 13

PMID 12477811

Citations 429

Authors

Robert Thimme

Stefan Wieland

Carola Steiger

John Ghrayeb

Keith A Reimann

Robert H Purcell

Francis V Chisari

Affiliations

Soon will be listed here.

Abstract

Although the CD4(+)- and CD8(+)-T-cell responses to the hepatitis B virus (HBV) are thought to be crucial for the control of HBV infection, the relative contribution of each T-cell subset as an effector of viral clearance is not known. To examine this question, we monitored the course of HBV infection in control, CD4-depleted, and CD8-depleted chimpanzees. Our results demonstrate that CD8(+) cells are the main effector cells responsible for viral clearance and disease pathogenesis during acute HBV infection, and they suggest that viral clearance is mediated by both noncytolytic and cytolytic effector functions of the CD8(+)-T-cell response.

Citing Articles

Intrahepatic CD161CD8+T Cell Recruitment Has a Pathogenetic Potential in Chronic HBV Infection.

Li J, Liu Q, Duan W, Duan Z, Liu F, Ruan M Immun Inflamm Dis. 2025; 13(1):e70118.

PMID: 39799583 PMC: 11725298. DOI: 10.1002/iid3.70118.

Tissue Determinants of Antiviral Immunity in the Liver.

Wohlleber D, Knolle P Z Gastroenterol. 2025; 63(1):65-72.

PMID: 39793603 PMC: 11723797. DOI: 10.1055/a-2365-3900.

Humoral, cellular immunity and efficacy of bioreactor propagated and inactivated Fowl adenovirus 8b adjuvanted with Montanide 71VG in broiler chickens.

Ugwu C, Hair-Bejo M, Nurulfiza M, Omar A, Ideris A J Adv Vet Anim Res. 2024; 11(3):693-702.

PMID: 39605767 PMC: 11590594. DOI: 10.5455/javar.2024.k819.

Unlocking CD8 T cell potential in chronic hepatitis B virus infection.

Fumagalli V, Iannacone M Nat Rev Gastroenterol Hepatol. 2024; 22(2):92-93.

PMID: 39551880 DOI: 10.1038/s41575-024-01015-x.

Nucleos(t)ide analogues potentially activate T lymphocytes through inducing interferon expression in hepatic cells and patients with chronic hepatitis B.

Ho A, Chang J, Lee S, Sie Z, Shih H, Yeh C Sci Rep. 2024; 14(1):25286.

PMID: 39455685 PMC: 11511960. DOI: 10.1038/s41598-024-76270-8.

References

Jonker M, Slingerland W, Treacy G, van Eerd P, Pak K, Wilson E . In vivo treatment with a monoclonal chimeric anti-CD4 antibody results in prolonged depletion of circulating CD4+ cells in chimpanzees. Clin Exp Immunol. 1993; 93(3):301-7. PMC: 1554916. DOI: 10.1111/j.1365-2249.1993.tb08176.x. View

Ferrari C, Penna A, Giuberti T, Tong M, Ribera E, Fiaccadori F . Intrahepatic, nucleocapsid antigen-specific T cells in chronic active hepatitis B. J Immunol. 1987; 139(6):2050-8. View

Battegay M, Moskophidis D, Rahemtulla A, Hengartner H, Mak T, Zinkernagel R . Enhanced establishment of a virus carrier state in adult CD4+ T-cell-deficient mice. J Virol. 1994; 68(7):4700-4. PMC: 236402. DOI: 10.1128/JVI.68.7.4700-4704.1994. View

Guidotti L, Martinez V, Loh Y, Rogler C, Chisari F . Hepatitis B virus nucleocapsid particles do not cross the hepatocyte nuclear membrane in transgenic mice. J Virol. 1994; 68(9):5469-75. PMC: 236947. DOI: 10.1128/JVI.68.9.5469-5475.1994. View

Kajino K, Jilbert A, Saputelli J, Aldrich C, Cullen J, Mason W . Woodchuck hepatitis virus infections: very rapid recovery after a prolonged viremia and infection of virtually every hepatocyte. J Virol. 1994; 68(9):5792-803. PMC: 236983. DOI: 10.1128/JVI.68.9.5792-5803.1994. View

Matloubian M, Concepcion R, Ahmed R . CD4+ T cells are required to sustain CD8+ cytotoxic T-cell responses during chronic viral infection. J Virol. 1994; 68(12):8056-63. PMC: 237269. DOI: 10.1128/JVI.68.12.8056-8063.1994. View

Rehermann B, Fowler P, Sidney J, Person J, Redeker A, Brown M . The cytotoxic T lymphocyte response to multiple hepatitis B virus polymerase epitopes during and after acute viral hepatitis. J Exp Med. 1995; 181(3):1047-58. PMC: 2191941. DOI: 10.1084/jem.181.3.1047. View

Guidotti L, Matzke B, Schaller H, Chisari F . High-level hepatitis B virus replication in transgenic mice. J Virol. 1995; 69(10):6158-69. PMC: 189513. DOI: 10.1128/JVI.69.10.6158-6169.1995. View

Guidotti L, Ishikawa T, Hobbs M, Matzke B, Schreiber R, Chisari F . Intracellular inactivation of the hepatitis B virus by cytotoxic T lymphocytes. Immunity. 1996; 4(1):25-36. DOI: 10.1016/s1074-7613(00)80295-2. View

10.

Rehermann B, Lau D, Hoofnagle J, Chisari F . Cytotoxic T lymphocyte responsiveness after resolution of chronic hepatitis B virus infection. J Clin Invest. 1996; 97(7):1655-65. PMC: 507230. DOI: 10.1172/JCI118592. View

11.

Penna A, Artini M, Cavalli A, Levrero M, Bertoletti A, Pilli M . Long-lasting memory T cell responses following self-limited acute hepatitis B. J Clin Invest. 1996; 98(5):1185-94. PMC: 507541. DOI: 10.1172/JCI118902. View

12.

Rehermann B, Chang K, McHutchinson J, Kokka R, Houghton M, Rice C . Differential cytotoxic T-lymphocyte responsiveness to the hepatitis B and C viruses in chronically infected patients. J Virol. 1996; 70(10):7092-102. PMC: 190761. DOI: 10.1128/JVI.70.10.7092-7102.1996. View

13.

Bertoletti A, DElios M, Boni C, De Carli M, Zignego A, Durazzo M . Different cytokine profiles of intraphepatic T cells in chronic hepatitis B and hepatitis C virus infections. Gastroenterology. 1997; 112(1):193-9. DOI: 10.1016/s0016-5085(97)70235-x. View

14.

Franco A, Guidotti L, Hobbs M, Pasquetto V, Chisari F . Pathogenetic effector function of CD4-positive T helper 1 cells in hepatitis B virus transgenic mice. J Immunol. 1997; 159(4):2001-8. View

15.

Jilbert A, Botten J, Miller D, Bertram E, Hall P, Kotlarski J . Characterization of age- and dose-related outcomes of duck hepatitis B virus infection. Virology. 1998; 244(2):273-82. DOI: 10.1006/viro.1998.9095. View

16.

Bertoletti A, Ferrari C, Fiaccadori F, Penna A, Margolskee R, Schlicht H . HLA class I-restricted human cytotoxic T cells recognize endogenously synthesized hepatitis B virus nucleocapsid antigen. Proc Natl Acad Sci U S A. 1991; 88(23):10445-9. PMC: 52945. DOI: 10.1073/pnas.88.23.10445. View

17.

Jilbert A, Wu T, England J, Hall P, Carp N, OConnell A . Rapid resolution of duck hepatitis B virus infections occurs after massive hepatocellular involvement. J Virol. 1992; 66(3):1377-88. PMC: 240860. DOI: 10.1128/JVI.66.3.1377-1388.1992. View

18.

Guilhot S, Fowler P, Portillo G, Margolskee R, Ferrari C, Bertoletti A . Hepatitis B virus (HBV)-specific cytotoxic T-cell response in humans: production of target cells by stable expression of HBV-encoded proteins in immortalized human B-cell lines. J Virol. 1992; 66(5):2670-8. PMC: 241021. DOI: 10.1128/JVI.66.5.2670-2678.1992. View

19.

Missale G, Redeker A, Person J, Fowler P, Guilhot S, Schlicht H . HLA-A31- and HLA-Aw68-restricted cytotoxic T cell responses to a single hepatitis B virus nucleocapsid epitope during acute viral hepatitis. J Exp Med. 1993; 177(3):751-62. PMC: 2190933. DOI: 10.1084/jem.177.3.751. View

20.

Bertoni R, Sette A, Sidney J, Guidotti L, Shapiro M, Purcell R . Human class I supertypes and CTL repertoires extend to chimpanzees. J Immunol. 1998; 161(8):4447-55. View