Cell-Mediated Immune Response to Liver Tissue Antigen and Hepatitis B Surface Antigen after Infection with Hepatitis B Virus in Humans

Tiku, M. L.; Beutner, Karl R.; Tiku, Katherine; Ogra, Pearay L.

doi:10.1093/infdis/138.5.587

Cited by 11 publications

(3 citation statements)

References 40 publications

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“…T-cell responses to viral antigens are undetectable in most patients with established chronic HBV infection, and asymptomatic carriers of HBV appear to be immunologically tolerant to HBV (11,14,21,22,(24)(25)(26)44). T-cell responses to HBV antigens have been detected in some chronically infected HBV patients but usually in association with transient exacerbation of chronic hepatitis resulting from modulation in viremia or seroconversion from HBV e antigen to antibody against HBV e antigen (13, 14, 21, 22, 24-26, 29, 30, 44, 45).…”

Section: Discussionmentioning

confidence: 99%

Deficiencies in the Acute-Phase Cell-Mediated Immune Response to Viral Antigens Are Associated with Development of Chronic Woodchuck Hepatitis Virus Infection following Neonatal Inoculation

Menne

Roneker

Roggendorf³

et al. 2002

J Virol

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In vitro proliferation of peripheral blood mononuclear cells was used to measure virus-specific cell-mediated immunity (vCMI) following neonatal woodchuck hepatitis virus (WHV) infection. Fifteen neonates were inoculated with the W8 strain of WHV. In 11, infection was resolved, and 4 became chronic carriers. Nineteen neonates were inoculated with the W7 strain and all became chronic carriers. Seven age-matched uninfected woodchucks served as controls. Virologic and vCMI profiles among the W8 and W7 infections were compared and related to the outcome of infection. Resolving woodchucks had robust, acute-phase vCMI to WHV antigens (core, surface, and x) and to several nonoverlapping core peptides. The acute-phase vCMI was associated temporally with the clearance of viral DNA and of surface antigen from serum at 14 to 22 weeks postinfection. In contrast, in approximately half of the W8 and W7 infections that progressed to chronicity, no significant acute-phase vCMI was detected. In the remaining carriers, acute-phase vCMI was observed, but it was less frequent and incomplete compared to that of resolved woodchucks. Serum viral load developed less rapidly in those carriers that had evidence of acute-phase vCMI, but it was still increased compared to that of resolving woodchucks. Thus, vigorous and multispecific acute-phase vCMI was associated with resolution of neonatal WHV infection. Absent or incomplete acute-phase vCMI was associated with the progression to chronic infection. By analogy, these results suggest that the onset of chronic hepatitis B virus (HBV) infection in humans may be associated with deficiencies in the primary T-cell response to acute HBV infection.Adult humans infected with the hepatitis B virus (HBV) usually undergo an acute infection followed by recovery (i.e., resolution). Progression to chronic HBV infection is unusual in adults but frequent among unvaccinated children born to HBV-carrier mothers. Chronic HBV infection is characterized by severe hepatic disease sequelae, including chronic hepatitis, cirrhosis of the liver, and hepatocellular carcinoma (reviewed in reference 2). The early immunologic mechanisms that predispose to the development of chronic HBV infection are not completely understood (reviewed in references 2, 3, and 15).Resolution of acute HBV infection is associated with the early induction of virus-specific, cell-mediated immunity (vCMI), which involves T helper (Th) cells and cytotoxic T lymphocytes. The successful cell-mediated immune response culminates in acute hepatitis, elimination of the virus from the liver, and subsequent recovery (reviewed in references 2, 3, and 32).

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Section: Discussionmentioning

confidence: 99%

Deficiencies in the Acute-Phase Cell-Mediated Immune Response to Viral Antigens Are Associated with Development of Chronic Woodchuck Hepatitis Virus Infection following Neonatal Inoculation

Menne

Roneker

Roggendorf³

et al. 2002

J Virol

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“…Therefore, HBsAg is likely to be the protective antigen. In AHB, development of cell-mediated immune reaction to HBsAg, such as migration inhibition activity (4 , 21), lymphocyte transformation activity (6,17,18,21), cytotoxicity to HBsAg expressing target cells (1,19), have been reported. The development of HB vaccine has made feasible clinical application of the HBsAg and delayed-type hypersensitivity skin reaction to HBsAg (HBs-DTH) has been recognized as a useful marker for the presence of cellular immune responsiveness to HBsAg (8,(12)(13)(14)22).…”

mentioning

confidence: 99%

Delayed‐Type Hypersensitivity Skin Reaction to HBsAg and Immunohistopathologic Study of Liver in Patients with Acute Type B Viral Hepatitis

Nagafuchi

Kashiwagi

Tsuji

et al. 1989

Microbiology and Immunology

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“…Blood specimens from these patients were also tested for LT to HB,Ag by using a whole-blood microculture assay that has been described elsewhere (24). Effects of interferon treatment.…”

mentioning

confidence: 99%

Effects of Interferon and Adenine Arabinoside Treatment of Hepatitis B Virus Infection on Cellular Immune Responses

Hafkin

Pollard

Tiku

et al. 1979

Antimicrob Agents Chemother

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Fifteen patients with chronic hepatitis B were treated with adenine arabinoside (Ara-A) or human leukocyte interferon (HLI). Cellular immune response to hepatitis B virus surface antigen and antigens prepared from herpes simplex virus, varicella zoster virus, and cytomegalovirus was measured by a lymphocyte blast transfornation assay and an assay for interferon production. Measurements were made before, during, and after antiviral treatment. Unlike patients convalescing from acute hepatitis B, only 2 of 15 patients with chronic hepatitis B had significant blast transformation to hepatitis B surface antigen. One such response occurred during the pretreatment period of HLI therapy, and the other was in a patient undergoing low-dose (<105 U/kg per day) HLI therapy. Mononuclear cell cultures were tested for interferon production in the presence of hepatitis B surface antigen. Cells from only 1 of 15 patients produced detectable levels of interferon. In contrast, all of these patients had normal cellular immune responses to herpesvirus antigens. Transformation responses to herpes antigens decreased three-to fivefold after patients were treated with >iO5 U of HLI per kg per day.Antiviral therapy with <105 U of HLI per kg per day or Ara-A did not produce a detectable depression of transformation response. Ara-A produced marked lymphocytopenia and a marked lymphocyte fragility after 5 or more days of therapy. In vitro Ara-A was toxic to lymphocytes at concentrations as low as 0.5 pg/ml. These changes in lymphocyte parameters may affect the outcome of antiviral therapy.In preliminary trials of human leukocyte interferon (HLI) and adenine arabinoside (Ara-A) administration in chronic hepatitis B virus (HBV) infection (CH/HB5Ag+), variable therapeutic responses were observed. Although some patients with CH/HB6Ag+ experienced rapid and prolonged depression of HBV markers such as Dane particle-associated deoxyribonucleic acid polymerase, others with apparently similar disease states (as measured by physical examination, HBV markers, and liver function tests) had less depression of HBV markers; these changes were observed only during therapy (12,21). Ara-A and HLI might influence immune cell function adversely and thereby produce the less durable antiviral response observed in some patients. Altematively, changes in immunity may occur only in certain patients and may not be a universal response.To

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Cell-Mediated Immune Response to Liver Tissue Antigen and Hepatitis B Surface Antigen after Infection with Hepatitis B Virus in Humans

Cited by 11 publications

References 40 publications

Deficiencies in the Acute-Phase Cell-Mediated Immune Response to Viral Antigens Are Associated with Development of Chronic Woodchuck Hepatitis Virus Infection following Neonatal Inoculation

Deficiencies in the Acute-Phase Cell-Mediated Immune Response to Viral Antigens Are Associated with Development of Chronic Woodchuck Hepatitis Virus Infection following Neonatal Inoculation

Delayed‐Type Hypersensitivity Skin Reaction to HBsAg and Immunohistopathologic Study of Liver in Patients with Acute Type B Viral Hepatitis

Effects of Interferon and Adenine Arabinoside Treatment of Hepatitis B Virus Infection on Cellular Immune Responses

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