Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using transgenic mice that replicate hepatitis B virus (HBV) at high levels in the liver as recipients of HBV-specific cytotoxic T lymphocytes (CTLs), we showed that the chemokines responsive to gamma-2/IFN-gamma inducible protein ([Crg2]IP-10) and monokine induced by interferon-gamma (Mig) are rapidly and strongly induced in the liver after CTL transfer. The transferred CTLs produce neither chemokine; rather, they activate (via the secretion of IFN-gamma) hepatocytes and nonparenchymal cells of the liver to produce (Crg2)IP-10 and Mig. Importantly, blocking these chemokines in vivo reduces the recruitment of host-derived lymphomononuclear cells into the liver and the severity of the liver disease without affecting the IFN-gamma-dependent antiviral potential of the CTLs. The finding that neutralization of these chemokines is associated with maintenance of antiviral effects but diminished tissue damage may be significant for the development of immunotherapeutic approaches for the treatment of chronic HBV infection.
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PMID:Blocking chemokine responsive to gamma-2/interferon (IFN)-gamma inducible protein and monokine induced by IFN-gamma activity in vivo reduces the pathogenetic but not the antiviral potential of hepatitis B virus-specific cytotoxic T lymphocytes. 1174 77

DNA immunization was used to compare the immunogenicity of hepatitis B virus S gene variants. Four recombinant plasmid DNAs containing the full-length virus genome with different S gene inserts were used to immunize BALB/c and C57/BL/6 mice. These inserts were cloned from 129L (residue 129, glutamine to leucine), 129H (residue 129, glutamine to histidine) 145R (residue 145, glycine to arginine) variants and the wild-type virus. The titer of hepatitis B virus core antibodies (anti-HBc) in immunized mice was used as the control for the efficiency of DNA immunization. Serum hepatitis B surface antibody (anti-HBs) titer and cytokines induced in splenocytes stimulated with hepatitis B surface antigen (HBsAg) were monitored as specific immune responses induced by different plasmid DNAs. 129L DNA induced significantly lower anti-HBs antibodies (IgG, IgG1, and IgG2a) and less interferon-gamma, compared to those in mice immunized with the 129H variant and the wild-type HBV DNA (p < 0.05). Computer modeling showed that a change from glutamine to leucine at 129 residue led to higher hydrophobicity and could result in decreased immunogenicity. Results indicate that DNA immunization can be used to compare the humoral and cellular immunogenicity among different HBV S variants.
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PMID:Comparing the immunogenicity of hepatitis B virus S gene variants by DNA immunization. 1179 65

Conflicting results obtained from animal studies suggest that B cells play a role in maintaining long-term T-cell memory and in skewing T-cell response toward a T-helper 2 (T(H)2) phenotype. X-linked agammaglobulinemia (XLA) is a genetic human disease characterized by the lack of circulating B cells due to the mutation of Bruton tyrosine kinase. This disease thus represents a unique model for studying the role of B lymphocytes in regulating T-cell functions in humans. To this aim, we analyzed hepatitis B envelope antigen (HBenvAg)-specific T-cell memory in a series of XLA patients vaccinated against hepatitis B virus (HBV). We found HBenvAg-specific T lymphocytes producing interferon-gamma, interleukin-4, or both in the peripheral blood of XLA patients up to at least 24 months after completing the standard anti-HBV immunization protocol. The HBenvAg-specific T-cell frequencies and the percentage of patients with these responses were not significantly different from healthy vaccinated controls. By combining cell purification and enzyme-linked immunospot assay, we found that effector CD27- T cells, which promptly produced cytokines in response to antigen (Ag), and memory-resting CD27+ T cells, which required Ag restimulation to perform their functions, were maintained in both XLA patients and controls for up to 24 months after the last vaccination boost. These data strongly suggest that B cells are not an absolute requirement for the generation of effective T-cell memory in humans, nor do they seem to influence T(H)1/T(H)2 balance.
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PMID:Long-lasting memory-resting and memory-effector CD4+ T cells in human X-linked agammaglobulinemia. 1187 89

Ultraviolet light exposure can impair immune responses that are not restricted to the exposed skin but is also found at other sites, i.e. systemic immunosuppression. Therefore, we investigated the UV-induced modulating effects on vaccination against hepatitis B in a mouse model. Two different mouse strains, BALB/c and C57B1/ 6, were vaccinated intramuscularly against hepatitis B. Mice were exposed to different doses of ultraviolet B (UVB) for five consecutive days on shaved back skin before the vaccination. Vaccination against hepatitis B induced cellular (delayed-type hypersensitivity [DTH] and lymphocyte stimulation test) as well as humoral immune responses in both mouse strains. The DTH responses in C57BB1/6 mice were statistically significantly higher compared with BALB/c mice. UVB exposure induced a dose-dependent suppression of cellular immunity in both strains of mice. C57B1/6 mice seemed to be more susceptible to this suppression. Anti-hepatitis B surface antibodies (total-Ig) were only marginally suppressed after UVB exposure. IgG2a and interferon-gamma levels, both indicators for Th1 immune response, were suppressed in both mouse strains after UVB exposure. In summary, UVB exposure induced a dose-dependent suppression of both cellular and humoral immune responses after hepatitis B vaccination, although the suppressive effects on humoral immunity were limited to IgG2a production. Susceptibility to UVB-induced immunomodulation depended on the strain of mice and their predilection for developing different T cell responses.
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PMID:UVB exposure impairs immune responses after hepatitis B vaccination in two different mouse strains. 1201 82

Adoptive therapy with antigen-specific T cells is a potential treatment against cancers and viral diseases. To establish a system to modify the genes of these cells to increase their effectiveness, we examined whether the combined use of retroviral vector, which only infects dividing cells, and in vitro sensitization of T cells with antigen-loaded dendritic cells (DCs) could selectively modify antigen-specific T cells with a bcl-2 gene. Human CD4(+) T cells were used as target cells. Autologous DCs transfected with genes of hepatitis B virus (HBV) stimulated a specific T cell proliferation. Importantly, these proliferating T cells were selectively transduced by a bcl-2-retrovirus, and CD25(+) T cells isolated from them contained higher levels of integrated provirus. To select bcl-2-transduced, activated T cells, cells were subjected to interleukin-2 (IL-2) withdrawal. In contrast to CD25(-) and mock-infected CD25(+) T cells, 70% of CD25(+) T cells transduced with bcl-2-retrovirus survived IL-2 withdrawal. These surviving T cells were demonstrated to contain integrated bcl-2 provirus and exhibited HBV-specific proliferation and interferon-gamma secretion. In addition, bcl-2 overexpression protected HBV-specific T cells from transforming growth factor (TGF)-beta-induced cell death. These results demonstrate the feasibility of our strategy in the generation of genetically modified antigen-specific CD4(+) T cells and show that bcl-2-transduced antigen-specific T cells survive IL-2 withdrawal and TGF-beta-induced apoptosis.
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PMID:Selective modification of antigen-specific CD4(+) T cells by retroviral-mediated gene transfer and in vitro sensitization with dendritic cells. 1213 48

Forty-four patients with chronic HBV and HCV were observed. Serum levels of interferon-gamma (IFN-gamma), interleukin-2 (IL-2), and soluble IL-2 receptor (IL-2r) were measured by enzyme immunoassay in 29 patients divided into 3 groups: group 1 (n = 9) with chronic HBV, group 2 (n = 9) with chronic HCV, and group 3 (n = 11) with mixed HBV + HCV infection. Control group consisted of 10 normal subjects without HBV, HCV, or HIV infection markers. The most informative of Th1 cytokines was IL-2r: its concentration was increased significantly (p < 0.01) in all patients with hepatitis B and/or C in comparison with the control. In addition, there was a trend to an increase in the mean concentrations of IL-2r from group 1 to groups 2 and 3. The concentrations of IFH-gamma and IL-2 did not differ significantly in the patients and controls. However, the concentrations of IFN-gamma were increased significantly (p < 0.01) in comparison with the control in 3 patients from group 1 and 4 patients from group 3 with more pronounced inflammation.
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PMID:[Th1-cytokines in chronic hepatitis B and C]. 1217 30

Insufficient stimulatory capacities of autologous dendritic cells (DC) may contribute in part to impaired T cell stimulation and therefore viral persistence in patients with chronic hepatitis B virus (HBV) infection. In order to characterize the antigen presenting functions of DC from chronic HBV carriers and controls antigen specific T cell responses were analysed. CD34+ peripheral blood progenitor cells were differentiated to immature DC in the presence of GM-CSF, IL-6/IL-6R fusion protein and stem cell factor. Proliferative CD4+ T cell responses and specific cytokine release were analysed in co-cultures of DC pulsed with HBV surface and core antigens or tetanus toxoid and autologous CD4+ T cells. Cultured under identical conditions DC from chronic HBV carriers, individuals with acute resolved hepatitis B and healthy controls expressed similar phenotypical markers but chronic HBV carriers showed less frequent and weaker HBV antigen specific proliferative T helper cell responses and secreted less interferon-gamma while responses to the tetanus toxoid control antigen was not affected. Preincubation with recombinant IL-12 enhanced the HBV specific immune reactivities in chronic HBV patients and controls. In conclusion, the weak antiviral immune responses observed in chronic hepatitis B may result in part from insufficient T cell stimulating capacities of DC. Immunostimulation by IL-12 restored the HBV antigen specific T cell responses and could have some therapeutical benefit to overcome viral persistence.
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PMID:Reduced virus specific T helper cell induction by autologous dendritic cells in patients with chronic hepatitis B - restoration by exogenous interleukin-12. 1229 60

Various cytokines and chemokines play a role in carcinogenesis. However, no study has previously been undertaken to investigate comprehensively the expressions of cytokines and chemokines in hepatoma cells. In this study, we determined which cytokines and chemokines are expressed in hepatoma cells. Recently, it was reported that the expressions of several chemokines could be increased by Fas stimulus in many normal and cancer cells. Therefore, we also investigated whether chemokines expression is regulated by Fas ligation. To address this issue, we performed RNase protection assays upon 13 cytokines and 8 chemokines genes in 10 human hepatoma cell lines, comprising 8 hepatitis B virus (HBV)-associated hepatoma cell lines. Transforming growth factor-beta2 (TGF-beta2) was found to be expressed in 8 HBV-associated hepatoma cell lines, and to be potently expressed in 5 cell lines; however, the mRNA expressions of interleukin-10 (IL-10), IL-12, interferon-gamma(IFN-gamma) and tumor necrosis factor-alpha(TNF-alpha) were not detected in any cell lines examined. Among the chemokines investigated in this study, IL-8 was expressed by 8 HBV- associated hepatoma cell lines, and monocyte chemoattractant protein-1 (MCP-1) by 7 HBV-associated hepatoma cell lines. However, the mRNA expressions of macrophage inflammatory protein-1alpha(MIP-1alpha), MIP-1beta, interferon-inducible protein-10 (IP-10), RANTES, lymphotactin and I-309 were either very weak or undetectable. Fas ligation did not increase chemokines expression in hepatoma cells. Conclusively, TGF-beta2, IL-8 and MCP-1 were overexpressed in HBV-associated hepatoma cells, and the expressions of chemokines were not increased by Fas ligation in human hepatoma cells.
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PMID:Expression patterns of cytokines and chemokines genes in human hepatoma cells. 1240 81

The functions of resident antigen-presenting cells (APC) may be compromised in inflammatory microenvironment of the host. However, little is known regarding the phenotype and function of the liver resident APC in this condition. This issue was addressed by evaluating the function of liver dendritic cells (DC) from mice with concanavalin-A-induced experimental hepatitis. In sharp contrast to normal mice, the expressions of MHC class II and CD86 antigens were not upregulated on liver DC from mice with hepatitis due to interactions with specific antigens like hepatitis B surface antigen and keyhole limpet hemocyanin. Accordingly, these DC were completely unable to induce proliferation of antigen-specific memory lymphocytes. Moreover, liver DC from mice with hepatitis produced significantly lower levels of interleukin-12 and interferon-gamma compared with those from control mice. The lack of antigen internalization capacity of liver DC from mice with hepatitis was evident from their low endocytosis capacity. These data indicate that impaired antigen capturing and T cell activating capacity of liver DC may contribute to low magnitude of antigen-specific immune responses in mice with experimental hepatitis.
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PMID:Inability of liver dendritic cells from mouse with experimental hepatitis to process and present specific antigens. 1278 6

The pathogenesis of hepatitis C virus-induced chronic liver disease is still poorly understood. Previous studies revealed enhanced hepatic expression of the Th1 prototype cytokine IFN-gamma in individuals with chronic hepatitis C. In accordance with several animal models of experimentally induced hepatitis, a Th1 lymphocyte driven inflammatory process, which involves newly infiltrated as well as resident monocytes/macrophages, has been proposed. An involvement of the interferon-gamma-inducible chemokine IP-10, which is chemoattractive for stimulated Th1 cells and monocytes, is also suggested. Using an HBV transgenic mouse model, a reduction of hepatic infiltration and liver disease was achieved recently by administration of antibodies directed against the interferon-gamma-inducible chemokine Mig and against IP-10. In the present study, expression of IP-10 was investigated both in serum and in the liver of patients with chronic hepatitis C and hepatitis B. Patients with liver diseases of non-viral etiologies served as controls. IP-10 expression was highest in hepatitis C. In chronic hepatitis C, but not in chronic hepatitis B nor in liver disorders unrelated to viral infections, IP-10 expression was strongly correlated with the amount of transcripts for IFN-gamma and to the amount of transcripts for the constitutively expressed macrophage derived cytokine IL-18. Hepatic inflammatory activity, however, was found to be associated more closely with IFN-gamma than with IP-10 or IL-18 mRNA expression. The data support the hypothesis that IP-10 is responsible for the recruitment of Th cells and monocytes in chronic hepatitis C, and suggest that its role in chronic hepatitis B is less determining. Moreover, they deliver additional support for the view that IFN-gamma still has to be considered as a mediator that determines the outcome of inflammation, e.g., via its ability to activate IL-18 expressing cells and to initiate a delayed type hypersensitivity reaction.
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PMID:Expression of the chemokine IP-10 correlates with the accumulation of hepatic IFN-gamma and IL-18 mRNA in chronic hepatitis C but not in hepatitis B. 1279 18


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