Immunology of hepatitis B infection

Jung, Maria–Christina; Pape, Gerd R.

doi:10.1016/s1473-3099(01)00172-4

Cited by 219 publications

(177 citation statements)

References 55 publications

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“…PBMCs resuspended at 1 Â 10 6 /mL in 96-well plates were stimulated with phytohemagglutinin (PHA) (1 lg/mL) or OKT3 (0.1 lg/ mL) for 5 days. 3 H-thymidine was then added to each well.…”

Section: Methodsmentioning

confidence: 99%

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Plasmacytoid dendritic cells induce efficient stimulation of antiviral immunity in the context of chronic hepatitis B virus infection

et al. 2012

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The immune control of hepatitis B virus (HBV) infection is essential for viral clearance. Therefore, restoring functional anti-HBV immunity is a promising immunotherapeutic approach to treatment of chronic infection. Plasmacytoid dendritic cells (pDCs) play a crucial role in triggering antiviral immunity through their ability to capture and process viral antigens and subsequently induce adaptive immune responses. We investigated the potential of pDCs to trigger antiviral cellular immunity against HBV. We used a human leukocyte antigen A (HLA-A)*0201 1 pDC line loaded with HLA-A*0201-restricted peptides derived from hepatitis B core/hepatitis B surface (HBc/HBs) antigens to amplify specific CD8 T cells ex vivo from chronic HBV patients and established a Hepato-HuPBL mouse model to address the therapeutic potential of the strategy in vivo. Stimulation of PBMCs or liver-infiltrating lymphocytes from HLA-A*0201 1 chronic HBV patients by HBc peptide-loaded pDCs elicited up to 23.1% and 76.1% HBV-specific CD8 T cells in 45.8% of cases. The specific T cells from the ''responder'' group secreted interferon-c, expressed CD107 upon restimulation, and efficiently lysed HBV antigen-expressing hepatocytes. Circulating hepatitis B e antigen (HBeAg) was found to distinguish the group of patients not responding to the pDC stimulation. The therapeutic efficacy of the pDC vaccine was evaluated in immunodeficient NOD-SCID b 2 m 2/2 mice reconstituted with HBV patients' PBMCs and xenotransplanted with human HBV-transfected hepatocytes. Vaccination of Hepato-HuPBL mice with the HBc/HBs peptide-loaded pDCs elicited HBVspecific T cells able to specifically lyse the transfected hepatocytes and reduce the systemic viral load. Conclusion: pDCs loaded with HBV-derived peptides can elicit functional virus-specific T cells. HBeAg appears to be critical in determining the outcome of immunotherapies in chronic HBV patients. A pDC-based immunotherapeutic approach could be of interest in attempts to restore functional antiviral immunity, which is critical for the control of the virus in chronic HBV patients. (HEPATOLOGY 2012;56:1706-1718 D espite increasing awareness and extensive vaccination campaigns, chronic hepatitis B infection remains a global health problem.

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“…PBMCs resuspended at 1 Â 10 6 /mL in 96-well plates were stimulated with phytohemagglutinin (PHA) (1 lg/mL) or OKT3 (0.1 lg/ mL) for 5 days. 3 H-thymidine was then added to each well.…”

Section: Methodsmentioning

confidence: 99%

“…3,4 Patients who manage to clear the virus elicit vigorous and efficient multispecific T cell responses. In contrast, patients who evolve toward chronic infection mount only weak and inappropriate immune responses.…”

mentioning

confidence: 99%

Plasmacytoid dendritic cells induce efficient stimulation of antiviral immunity in the context of chronic hepatitis B virus infection

et al. 2012

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“…Worldwide, 350 million people suffer from chronic HBV infection, and approximately 1 million people die annually from HBV-related liver disease. 1,2 T helper 1 type cytokines such as interferon ␥ (IFN-␥) and interleukin 2 are involved in cell-mediated immunity and play a crucial role in the protection against intracellular pathogens, including HBV. 3 In patients with an acute self-limiting HBV infection, a multispecific CD4 ϩ and CD8 ϩ T-cell response with a type 1 cytokine profile is important for control of the infection.…”

Section: H Epatitis B Virus (Hbv) Is a Common Noncyto-mentioning

confidence: 99%

Regulatory T cells contribute to the impaired immune response in patients with chronic hepatitis B virus infection

et al. 2005

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Chronic hepatitis B virus (HBV) infection is H epatitis B virus (HBV) is a common noncyto-pathic DNA virus. Infection with HBV in adults results frequently in a self-limiting, acute hepatitis, which confers protective immunity and causes no further disease. In 10% of infected adults, HBV leads to a chronic infection. Chronic HBV infection is an important risk factor for the development of cirrhosis and hepatocellular carcinoma. Worldwide, 350 million people suffer from chronic HBV infection, and approximately 1 million people die annually from HBV-related liver disease. 1,2 T helper 1 type cytokines such as interferon ␥ (IFN-␥) and interleukin 2 are involved in cell-mediated immunity and play a crucial role in the protection against intracellular pathogens, including HBV. 3 In patients with an acute self-limiting HBV infection, a multispecific CD4 ϩ and CD8 ϩ T-cell response with a type 1 cytokine profile is important for control of the infection. 4 These multispecific T-cell responses are maintained for decades after clinical recovery. 5 In contrast, patients with a chronic HBV infection lack such a vigorous multispecific response. These patients have a weak or undetectable virus-specific T-cell response. 4 The precise mechanism responsible for this T-cell hyporesponsiveness or tolerance is still unknown. One scenario that has not been explored in relation to chronic HBV infection is the potential role of host-mediated immunosuppressive mechanisms that might be activated in the face of persistent antigenic exposure.

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“…Liver damage during HBV infection is thought to be mediated by the host cellular immune response to viral antigens (4,5). Persistent carriers of HBV, however, show a severe HBV-specific T-cell dysfunction with low levels of antiviral cytokines and impaired cytotoxic T lymphocytes activity (6,7).…”

Section: Introductionmentioning

confidence: 99%

Blockade of Tim-3 Pathway Ameliorates Interferon-γ Production from Hepatic CD8+ T Cells in a Mouse Model of Hepatitis B Virus Infection

Hou

Zhang

et al. 2009

Cell Mol Immunol

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Immunology of hepatitis B infection

Cited by 219 publications

References 55 publications

Plasmacytoid dendritic cells induce efficient stimulation of antiviral immunity in the context of chronic hepatitis B virus infection

Plasmacytoid dendritic cells induce efficient stimulation of antiviral immunity in the context of chronic hepatitis B virus infection

Regulatory T cells contribute to the impaired immune response in patients with chronic hepatitis B virus infection

Blockade of Tim-3 Pathway Ameliorates Interferon-γ Production from Hepatic CD8+ T Cells in a Mouse Model of Hepatitis B Virus Infection

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