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Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The fine specificity of the human T cell response to the hepatitis B virus core antigen (HBcAg) was investigated in 23 patients with acute hepatitis B virus (HBV) infection using a panel of short synthetic peptides covering the entire core region. An immunodominant T cell epitope which was recognized by all except one patient, was identified within the core sequence 50-69. Two further important T cell recognition sites were represented by the amino acid sequences 1-20 and 117-131, which were stimulatory for the T cells of 69% and 73% of the patients, respectively. T cell recognition of the synthetic peptides was HLA class II restricted because the peptide-induced T cell proliferation was inhibited by anti-HLA class II but not by anti-HLA class I monoclonal antibodies. These findings may be relevant to the development of future preventive and therapeutic strategies against HBV infection.
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PMID:Fine specificity of the human T cell response to hepatitis B virus core antigen. 128 May 6

To analyze the hepatitis B virus (HBV)-specific cytotoxic T-cell (CTL) response during acute and chronic viral hepatitis, target cells that express HBV-encoded antigens in the context of the appropriate HLA restriction element must be available for each subject studied. Since HBV is not infectious for human cells in vitro, such target cells must be produced by DNA-mediated gene transfer into cultured human primary cells or cell lines. For this purpose, we have developed a panel of Epstein-Barr virus-based episomal expression vectors containing each of the HBV open reading frames under the transcriptional control of the simian virus 40 early promoter. Transfection of Epstein-Barr virus-immortalized B-cell lines with this panel of recombinants consistently leads to stable expression of the HBV envelope, nucleocapsid, and polymerase proteins. The HBV X gene product is transiently expressed following transfection, but stable expression of this protein cannot be maintained on a long-term basis. To assess the suitability of this system for the identification of HBV-specific CTL in humans, a panel of EBO-HBV transfectants of defined HLA haplotype was used to monitor the HBV-specific CTL response in a patient with acute viral hepatitis type B. Transfectants that stably express the HBV nucleocapsid (core) antigen were found to serve as excellent targets for the detection of HLA class I-restricted CTL that recognize endogenously synthesized HBV core antigen in this patient; they were also successfully used to stimulate the specific expansion of these CTL in vitro.
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PMID: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. 131 93

HLA class I display on hepatitis B virus (HBV)-infected hepatocytes is important for limiting HBV infection. However, the effect of HBV replication on HLA class I expression on host cells has not been determined. Since acyclovir is known to inhibit HBV replication of the novel cell line HB611, which was transfected with HBV genome using human hepatoblastoma cells as the recipient and continuously replicates HBV DNA, we analyzed HLA class I expression on acyclovir-treated HB611 by quantitative flow cytometry. The results demonstrated that acyclovir treatment clearly increases the level of HLA class I on HB611, and suggested that HBV replication inhibits expression of HLA class I on infected hepatocytes. This effect of HBV replication on the host cell may be a means by which HBV evades immune surveillance to maintain chronic infection.
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PMID:Enhanced expression of HLA class I by inhibited replication of hepatitis B virus. 132 97

Review of the relationship between the degree of immunosuppression and malignancy in patients on immunosuppressive drugs or immunosuppressed by HIV infection, postoperative blood transfusion or pregnancy provides the most convincing evidence of the importance of intact T cell immunity in resistance to cancer. Defective HLA class I and II antigen expression on tumours arising in non-immunosuppressed individuals and correlation of these changes with increased malignancy and diminished TIL provide the most convincing evidence that one factor necessary to ensure survival of most spontaneous tumours is mutation that enables tumour cells to escape rejection by cytotoxic T cells. These changes are less frequent in tumours in immunosuppressed patients, and preliminary data suggest that use of cytokine therapy is more successful in these tumours and the one in five spontaneous tumours demonstrating normal expression of HLA antigens and high levels of T cell infiltration. These observations suggest that future use of this therapy should be focused on these cases. All modalities of cancer therapy except hormone therapy (ie surgery, radiotherapy and chemotherapy) suppress immune responses. Defects of HLA antigen expression are less marked in early cancer. Combinations of immunotherapy with conventional treatment at presentation, including hormone therapy in view of data demonstrating regeneration of the thymus after castration, needs further investigation. Preliminary results from randomized trials involving nearly 300 individuals accidentally exposed to carcinogens demonstrated nearly 60% reduction of incidence of malignancy at 5 years in the arm receiving non-specific immunotherapy. If confirmed, such an approach might be more cost-effective as an approach for cancer prevention than organ specific cancer screening or vaccination against cancer associated viruses such as hepatitis B or papillomaviruses.
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PMID:T cell immune response to cancer in humans and its relevance for immunodiagnosis and therapy. 142 23

Knowledge of hepatitis B immunopathogenesis has greatly improved in the last few years thanks to the development of new methods of lymphocyte culture and the introduction of molecular techniques in the study of the cell-mediated antiviral immune responses. Some of the immune mechanisms likely responsible for liver cell injury and viral clearance during hepatitis B have recently been characterized. By using synthetic peptides and high efficiency recombinant expression vectors. HLA class I restricted cytotoxic T cells specifically able to recognize the nucleocapsid antigen of the hepatitis B virus (HBV) have been isolated from the blood of patients with acute self-limited hepatitis B. The observation that this cytotoxic response is lacking or very weak in chronic patients who do not succeed in clearing the virus suggests a major role for cytotoxic T cells in terminating virus infection. Similar behaviour is shown by HLA class II restricted CD4+ T cells which express much stronger levels of response to HBV nucleocapsid antigens in acute than in chronic HBV infection. Whether these defective responses in chronic patients are due to an actual lesion of the host's immune system or to viral mutations affecting immune surveillance and thereby allowing virus escape, still remain open issues. A definitive answer to these questions will, we hope, provide the appropriate tools to devise effective immune therapies against chronic HBV infection.
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PMID:[The immunopathogenesis of hepatitis B]. 145 54

Knowledge of the immune effector mechanisms responsible for clearance of hepatitis B virus (HBV)-infected cells has been severely limited by the absence of reproducible systems to selectively expand and to characterize HBV-specific cytotoxic T lymphocytes (CTLs) in the peripheral blood of patients with viral hepatitis. By using a strategy involving sequential stimulation with HBV nucleocapsid synthetic peptides followed by autologous, or HLA class I-matched, HBV nucleocapsid transfectants, we now report the existence of CTLs able to lyse target cells that express endogenously synthesized HBV nucleocapsid antigen in the peripheral blood of patients with acute viral hepatitis B. The CTL response is HLA-A2 restricted, mediated by CD8-positive T cells, and specific for a single epitope, located between amino acid residues 11 and 27 of HBV core protein; these residues are shared with the secretable precore-derived hepatitis B e antigen. Equivalent lysis of target cells that express each of these proteins suggests that their intracellular trafficking pathways may intersect. The current report provides definitive evidence that HLA class I-restricted, CD8-positive CTLs that recognize endogenously synthesized HBV nucleocapsid antigen are induced during acute HBV infection in humans and establishes a strategy that should permit a detailed analysis of the role played by HBV-specific CTLs in the immunopathogenesis of viral hepatitis.
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PMID:HLA class I-restricted human cytotoxic T cells recognize endogenously synthesized hepatitis B virus nucleocapsid antigen. 166 Jan 37

The absence of readily manipulable experimental systems to study the cytotoxic T lymphocyte (CTL) response against hepatitis B virus (HBV) antigens has thus far precluded a definitive demonstration of the role played by this response in the pathogenesis of liver cell injury and viral clearance during HBV infection. To circumvent the problem that HBV infection of human cells in vitro for production of stimulator/target systems for CTL analysis is not feasible, a panel of 22 overlapping synthetic peptides covering the entire amino acid sequence of the HBV core (HBcAg) and e (HBeAg) antigens were used to induce and to analyze the HBV nucleocapsid-specific CTL response in nine patients with acute hepatitis B, six patients with chronic active hepatitis B, and eight normal controls. By using this approach, we have identified an HLA-A2-restricted CTL epitope, located within the NH2-terminal region of the HBV core molecule, which is shared with the e antigen and is readily recognized by peripheral blood mononuclear cells from patients with self-limited acute hepatitis B but less efficiently in chronic HBV infection. Our study provides the first direct evidence of HLA class I-restricted T cell cytotoxicity against HBV in humans. Furthermore, the different response in HBV-infected subjects who successfully clear the virus (acute patients) in comparison with patients who do not succeed (chronic patients) suggests a pathogenetic role for this CTL activity in the clearance of HBV infection.
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PMID:Cytotoxic T lymphocytes recognize an HLA-A2-restricted epitope within the hepatitis B virus nucleocapsid antigen. 172 Aug 13

This paper reviews the main necro-inflammatory liver lesions observed in chronic viral hepatitis B and their apparent immunological mechanisms. Focal necrosis seems to represent the mechanism for clearance of virus replicating hepatocytes by cytotoxic T lymphocytes under HLA class I restriction and with hepatitis B virus nucleocapsid antigens as target antigen. Piecemeal necrosis involves CD8+ lymphocytes, possibly with hepatocellular membrane autoantigens as target antigen. Confluent lytic necrosis (bridging hepatic necrosis) presumably results from humoral immune mechanisms. Focal necrosis, piecemeal necrosis and confluent lytic necrosis determine the extent of necro-inflammatory activity in liver biopsy specimens, classified as chronic persistent hepatitis (low activity) or chronic active hepatitis (high activity). The extent of necro-inflammatory activity fluctuates during the natural course of chronic viral hepatitis B: from low activity during the viral replicative phase, through high activity in the viral elimination phase, into low activity again in the ensuing viral integration phase. The role of HLA antigens, intercellular adhesion molecules, cytokines and accessory antigen presenting cells is emphasized.
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PMID:Immunopathology of chronic viral hepatitis. 190 15

In a chimpanzee model of acute type B hepatitis, at the time of onset of hepatitis B virus replication and before the development of immunity to hepatitis B virus, interferon is present in the plasma. This is followed by an increase in the display of HLA class I, but not class II proteins, on the hepatocyte membrane. In chronic hepatitis B virus infection, there is a low density of HLA class I protein display on the infected hepatocyte. Administration of alpha-interferon enhances HLA display and in many cases is followed by a transaminase elevation, seroconversion of HBe antigen to antibody and disappearance of hepatitis B virus DNA from serum, changes implying clearance of infected hepatocytes. Successful response to interferon therapy may be predicted by a rapidly rising serum beta 2-microglobulin, a component of the HLA class I molecule, during the first 2 weeks of therapy, before the rise in transaminases.
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PMID:HLA class I antigens on the hepatocyte membrane during recovery from acute hepatitis B virus infection and during interferon therapy in chronic hepatitis B virus infection. 242 27

In order to elucidate the mechanism by which HLA antigens expression is induced or enhanced on the injured or transformed hepatocytes, we have made in vitro studies using human hepatic tumor-derived cell lines as a model system. In the present study, PLC-PRF-5 cells that have the integrated form of hepatitis B virus genome in DNA were treated with 5-azacytidine (5-azaC) in combination with gamma-interferon (IFN-gamma) or dimethyl sulfoxide (DMSO). HLA antigens on the cell surface were quantitated by using a modified cell-ELISA method. As a result, it was demonstrated that DMSO- or IFN-gamma-treatment enhanced expression of HLA class I antigens on the cell surface. In addition, enhanced expression of the antigens on PLC-PRF-5 cells treated with 5-azaC in combination with IFN-gamma or DMSO represented a synergistic effect of these inducers on HLA class I antigens expression although no changes in HLA antigens expression were induced after 5-azaC-treatment alone in short-term experiments. Furthermore, an indirect immunofluorescent analysis of hepatitis B surface antigen on the cells demonstrated increased expression of the antigen after 5-azaC-treatment alone. HLA class II antigens and hepatitis B core antigen were not induced even after those treatments and also not after a long-term experiment. These results might indicate possible modulation of HLA class I and hepatitis B virus antigens expression on the cultured cells by a DNA hypomethylating agent, 5-azaC.
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PMID:Synergistic effect of 5-azacytidine and gamma-interferon or dimethyl sulfoxide on expression of HLA class I antigens by PLC-PRF-5 cells. 246 98


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