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)

Two groups of subjects receiving two different doses of yeast-derived recombinant hepatitis B surface antigen (rHBsAg) (10 micrograms Gen-HB-Vax, Merck Sharp and Dohme and 20 micrograms Engerix-B, Smith Kline and French) were investigated for in vitro specific humoral and cellular response to the native protein. In vitro proliferative response was dependent on the following critical variables: (1) antigen-specific precursor lymphocytes were present in the peripheral blood for a very short time; (2) the number of circulating specific precursors was dependent on the dose of HBsAg used for vaccination; (3) the presence of antigen-presenting cells was necessary to obtain a blastogenic response in vitro. In vitro proliferation was enhanced by the addition of recombinant interleukin 2 (rIL-2). Spontaneous and stimulated (anti-CD3, pokeweed mitogen) anti-HBs antibody production in vitro was obtained in only eight out of 20 subjects after the fourth boost. Although a different immunogenicity of the two vaccines cannot be excluded, these data strongly suggest that T and B cells responsive to HBsAg present different kinetics of recirculation in the peripheral blood, depending on the antigen dose used for immunization.
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PMID:Cellular response and anti-HBs synthesis in vitro after vaccination with yeast-derived recombinant hepatitis vaccine. 138 54

Peripheral blood mononuclear cells (PBMC) from 25 patients with chronic hepatitis B were tested for the presence of free monomeric hepatitis B virus (HBV) DNA migrating as a single 3.2 Kb band by Southern blot analysis. The PBMC were cultured for 7 days in the presence of phytohemagglutinin (PHA) or concanavalin A (ConA) both of which yielded a proliferative response. By contrast, both bacterial lipopolysaccharide (LPS) and interleukin 2 (IL2) failed to do so. Dot blot assays were used to monitor HBV DNA level increase within PBMC. Following mitogen exposure HBV DNA levels increased above pre-stimulation levels in 19/25 PHA cultures, 6/15 ConA cultures, 1/15 LPS cultures, and 1/15 IL2 cultures. In 15 patients, Southern blot analysis was carried out before and after PHA exposure. In 13/15 cases, a single 3.2 Kb band was observed in unstimulated cultures as well as in PHA cultures even though PHA induced a HBV DNA increase. One case exhibited bands migrating faster than the 3.2 Kb signal, compatible with replicating intermediates and one case provided evidence of viral concatemers within PBMC after PHA stimulation. No HBV DNA was detected in the culture supernatants. The increase of HBV DNA level in PBMC induced by mitogen was strongly associated with an increase in HBV DNA expression (HBV RNA and HBs antigen). These studies indicate that HBV DNA present in human PBMC does represent a potential reservoir for infection with endogenous reactivation following PBMC activation.
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PMID:Phytohemagglutinin and concanavalin A activate hepatitis B virus in peripheral blood mononuclear cells of patients with chronic hepatitis B virus infection. 140 24

Lipid peroxide (Lpo) of peripheral blood lymphocytes was measured with fluorescent method in 69 cases of hepatitis B and 35 normal subjects. The lymphocyte Lpo in patients with chronic active and severe hepatitis B was much higher than that in the normal subjects (P less than 0.01). Furthermore, the value of lymphocyte Lpo showed negative correlation with the number of peripheral blood lymphocytes (P less than 0.05) and the activity of interleukin 2 (P less than 0.01) in patients with severe hepatitis B. It also showed negative correlation with the latter in cases with chronic active hepatitis B (P less than 0.05). These data suggest that lipid peroxidation of peripheral blood lymphocytes may be one of the causes of immune dysfunction in patients with hepatitis B.
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PMID:[Determination of lymphocyte lipid peroxide in patients with hepatitis B and its immunological significance]. 196 49

We examined the influence of uremic serum on antigen receptor triggered T cell proliferation in dialysis patients with impaired immune function, i.e., 12 nonresponders to hepatitis B vaccination. The dialysis patients showed a monocyte dysfunction and an increased responsiveness to interleukin 2 (IL-2) according to our previous findings. In vitro the addition of IL-2 completely reconstituted the defect. Uremic serum inhibited monocyte-dependent T cell proliferation of patients and of healthy controls. Contrary, monocyte-independent steps of T cell proliferation were not impaired by uremic serum. When IL-2 was added to cultures, the T cell proliferation in the presence of uremic serum was even enhanced. We conclude that uremic immunodeficiency may be enhanced by soluble factors present in uremic serum which inhibit monocyte-dependent steps of T cell proliferation.
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PMID:Uremic serum inhibits monocyte-dependent, but not interleukin-2-dependent steps of T cell proliferation. 224 71

Children with uncontrolled autoimmune chronic active hepatitis have increased numbers of activated T lymphocytes expressing interleukin 2 receptors (IL2R). A soluble form of IL2R has recently been described whose proposed role is to downregulate T cell activation by competing for interleukin 2. We investigated whether a deficiency of soluble IL2R could account for the high concentrations of IL2R positive T lymphocytes in autoimmune chronic active hepatitis. Soluble IL2R was measured by enzyme-linked immunosorbent assay in the serum of 16 children with autoimmune chronic active hepatitis, eight with chronic liver disease due to hepatitis B virus infection, seven with Wilson's disease, nine with alpha 1 antitrypsin deficiency, and 15 healthy age matched controls. Soluble IL2R concentration was significantly higher in patients with autoimmune chronic active hepatitis than in healthy controls (mean (SEM) 475 (75) U/ml, 145 (8) U/ml respectively, p less than 0.01). Eleven patients who had active disease had significantly higher soluble IL2R concentrations (590 (89) U/ml) than the five cases with inactive disease (220 (36) U/ml, p less than 0.01). No difference was found between the controls and the patients with chronic liver disease due to hepatitis B infection, Wilson's disease, and alpha 1 antitrypsin deficiency. Percentages and absolute numbers of surface IL2R positive T cells as detected by immunofluorescence were significantly higher in the patients with autoimmune chronic active hepatitis (11.8% (1); 274/microliters (31)) than in controls (0.2% (0.1); 5/microliters (2), p less than 0.001), the highest values being found in those with uncontrolled disease. A significantly positive correlation was observed between concentrations of soluble IL2R and the percentage of T cells expressing IL2 receptors (r=0.67, p<0.001). These results indicate that the high levels of IL2R positive T lymphocytes characteristic of autoimmune chronic active hepatitis are not due to a deficiency of soluble IL2 receptors.
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PMID:Soluble interleukin 2 receptors in autoimmune chronic active hepatitis. 237 74

By using a preparation of inactivated rabies virus, the blood mononuclear cells from five rabies vaccine recipients were stimulated in vitro in the presence of interleukin 2. T cell lines that displayed significant proliferative responses to whole rabies virus and to preparations of rabies glycoprotein and nucleocapsid were obtained from all the individuals. Other antigens, such as diphtheria and tetanus toxoids, influenza A virus, hepatitis B surface antigen, and serum albumin, failed to induce the proliferation of the T cell lines. One of these rabies-specific T cell lines was found to proliferate in response to rabies antigens only when the antigen-presenting cells expressed homologous HLA-DR antigens. The use of mouse monoclonal antibodies specific for human T cell surface markers revealed that most of the cells of these rabies-reactive lines were of the helper/inducer class of T lymphocytes. Stimulation of the T cell lines with the rabies antigens induced the production of interferon-gamma, a lymphokine with potent antiviral activity. Several T cell clones were isolated from two of these cell lines, and most of them appeared to be specific for the antigenic components of the viral nucleocapsid. Two T cell clones specific for the rabies glycoprotein were also isolated from one of these lymphocyte interleukin 2-dependent lines. Further in vitro studies with rabies-specific T cells could help us to understand in more depth the role of regulatory T cells in the human immune response to rabies virus.
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PMID:Isolation and characterization of human T cell lines and clones reactive to rabies virus: antigen specificity and production of interferon-gamma. 241 20

We have previously reported the establishment and preliminary characterization of polyclonal hepatitis B virus (HBV) nucleoprotein (HBcAg)-specific CD4+ and CD8+ T cell lines derived from the hepatic lymphomononuclear cell infiltrate of several patients with chronic active hepatitis B. The isolated subsets from these lines were specifically activated by HBcAg and displayed antigen-specific help and suppression with respect to proliferation of the alternate subset. One of these lines was recently cloned by limiting dilution, and four HBcAg-specific CD3+ CD4+ CD8-DR+ T cell lines were produced that had a 95.3% likelihood of monoclonality. Antigenic specificity was confirmed by dose-dependent, HLA class II (DR)-restricted proliferation in response to recombinant and human serum-derived HBcAg and the lack of proliferation to HBV envelope antigens (HBsAg and pre-S(2)Ag). All cloned lines were interleukin 2 dependent, produced interferon-gamma in an antigen-specific manner, and provided antigen-specific help to autologous B cells with respect to anti-HBc production. We conclude that HBcAg-specific, HLA-class II restricted helper T cells capable of inducing antigen-specific functional responses by autologous B lymphocytes and T lymphocytes are present at the site of viral antigen synthesis and hepatocellular injury in HBV infection.
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PMID:Functional characterization of cloned intrahepatic, hepatitis B virus nucleoprotein-specific helper T cell lines. 243 90

Hepatitis B virus nucleocapsid particles (HBcAg) can function as a T cell-independent antigen when injected into athymic mice. However, immunization of euthymic mice with HBcAg results in dramatically increased anti-HBc titers. Therefore we have examined the murine T cell response to HBcAg in terms of immunogenicity, the influence of H-2-linked genes, and the fine specificity of T cell recognition using synthetic peptide analogs. The HBcAg was shown to be an extremely efficient immunogen in terms of T cell activation as measured by the in vivo dose required to induce T cell sensitization (1.0 microgram), and the minimal in vitro concentration required to elicit interleukin 2 (IL 2) production (0.03 ng/ml). The degree of T cell immunogenicity of HBcAg and its ability to directly activate B cells most likely explain the enhanced humoral response to HBcAg in euthymic mice and HBV-infected patients. The influence of H-2-linked genes on the humoral response to HBcAg was discernable, and high responder (H-2k,s,d), intermediate responder (H-2b,f), and low responder (H-2p) haplotypes were identified. The H-2-linked regulation of the T cell response correlated with in vivo anti-HBc production. Examination of the fine specificity of T cell recognition revealed HBcAg-specific T cells from a variety of strains recognize multiple but distinct sites within the HBcAg/HBeAg sequence. T cell recognition sites were defined by small (16 to 21 residue) synthetic peptides. Each strain recognized a predominant T cell determinant, and the fine specificity of this recognition process was dependent on the H-2 haplotype of the responding strain. For example H-2s,b strains recognized p120-140, H-2f,q strains recognized p100-120, and H-2d mice recognized p85-100 predominantly. Because these sequences are common to both HBcAg and a nonparticulate form of the antigen termed HBeAg, these results indicate that HBcAg and HBeAg are highly cross-reactive at the T cell level although they are serologically distinct. These findings may have clinical relevance, because T cell sensitization to HBeAg and the subsequent seroconversion to anti-HBe status correlates with viral clearance during hepatitis B infection.
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PMID:Immune response to hepatitis B virus core antigen (HBcAg): localization of T cell recognition sites within HBcAg/HBeAg. 2344 29

The present study was undertaken to examine early T lymphocyte activation in chronic hepatitis B virus (HBV) carriers. Nineteen hepatitis B surface antigen-positive patients (eight with liver cirrhosis and 11 with chronic hepatitis) and 18 healthy controls were studied in a period free of other infection. Mitogen-stimulated cellular interleukin 2 receptor expression, soluble interleukin 2 receptor release, and interleukin 2 production were studied in peripheral blood mononuclear cells cultured for 24 h. No difference was demonstrated between the patients and healthy controls in the cellular interleukin 2 receptor expression, soluble interleukin 2 receptor release, and interleukin 2 production. Pokeweed mitogen-stimulated interleukin 2 production in lymphocytes from cirrhotic patients was significantly lower than that of the noncirrhotic patients. However, the cellular and soluble interleukin 2 receptor levels did not differ between the two groups of chronic HBV carriers. Despite the fact that it has been suggested that autoreactive T cells have a role in mediating the development of chronic liver diseases associated with HBV infection, this study fails to demonstrate a defective T lymphocyte activation in these patients. The observed reduction of interleukin 2 production from activated lymphocytes may be related to the severity of liver impairment, rather than the HBV infection itself.
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PMID:T lymphocyte activation in chronic hepatitis B infection: interleukin 2 release and its receptor expression. 259 55

This report describes a study of in vitro proliferative and antibody responses to the hepatitis B virus surface antigen (HBsAg) of lymphocytes from chronic HBsAg carriers, subjects with naturally acquired immunity, and responders to the hepatitis B vaccine. Peripheral blood T and B lymphocytes were cultured with a wide range of concentrations of HBsAg (0.025-250 ng/ml). We were unable to detect HBsAg-specific proliferation or antibody synthesis in any of the subject groups studied, despite the use of a range of antigen concentrations, cell ratios and culture periods. The addition of recombinant interleukin 2 (rIL-2) or T cell growth factor at either initiation or day 3 of culture enhanced proliferative responses, but in an antigen-independent manner. In contrast to the proliferation observed following the addition of IL-2, the absence of responses to specific antigen suggest there may be low numbers of HBsAg-specific precursors in the peripheral blood.
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PMID:HBsAg-induced antigen-specific T and B lymphocyte responses in chronic hepatitis B virus carriers and immune individuals. 278 46


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