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)

The inability of hepatitis B virus (HBV) transgenic mice, which express abundant hepatitis B surface antigen (HBsAg) in sera from the neonatal period onwards, to produce antibody to HBsAg (anti-HBs) is considered to be due to defective function of lymphocytes. The defective function is thought to result from neonatal tolerance because antigenic challenge during the neonatal period is considered to be a tolerogenic event rather than an immunogenic one. However, a series of mixed culture experiments in vitro showed that lymphocytes taken from transgenic mice that had been injected with HBsAg in complete Freund's adjuvant (CFA) constitutively produced anti-HBs when cultured with dendritic cells from age-, sex- and major histocompatibility complex (MHC)-matched normal mice, but not when cultured with dendritic cells from transgenic mice. The expression of major histocompatibility complex (MHC) class II and B 7.2 (CD86) antigens on dendritic cells was significantly lower in transgenic mice compared with the same from the normal mice (P < 0.05). Treatment of transgenic mice with interferon-gamma (IFN-gamma) resulted in up-regulation of MHC class II on dendritic cells, and lymphocytes from HBsAg-injected transgenic mice produced anti-HBs in vitro when cultured with dendritic cells from IFN-gamma-treated transgenic mice, but not when cultured with the dendritic cells from untreated transgenic mice. These experiments have shown that defective function of antigen-presenting cells (APC), not immunogenic tolerance, is responsible for the inability of murine HBV-carriers to produce anti-HBs. Production of anti-HBs by lymphocytes from HBsAg-injected transgenic mice in the presence of dendritic cells that express higher levels of MHC class II and CD86 antigens has inspired optimism that a more effective vaccine therapy can be developed for chronic HBV-carriers, injecting vaccine containing HBsAg with modulator(s) of APC function of dendritic cells.
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PMID:Production of antibody to hepatitis B surface antigen (anti-HBs) by murine hepatitis B virus carriers: neonatal tolerance versus antigen presentation by dendritic cells. 949 91

The murine melanoma cell line B16.F10 (H-2b) was used to study specific T cell responses that reject tumors. Stable B16 transfectants were established that express viral Ags, either the hepatitis B surface Ag (HBsAg) or the large tumor Ag (T-Ag) of SV40. B16 cells and their transfected sublines were CD40+ CD44+ but expressed no (or low levels of the) costimulator molecules CD154 (CD40L), CD48, CD54, CD80, and CD86. Surface expression of MHC class I (Kb, Db) and class II (I-Ab) molecules by B16 cells was low, but strikingly up-regulated by IFN-gamma. CD95 (Fas) and CD95 ligand (CD95L (FasL)) were "spontaneously" expressed by B16 cells growing in vitro in serum-free medium; these markers were strikingly up-regulated by IFN-gamma. B16 cells coexpressing CD95 and CD95L were irreversibly programmed for apoptosis. In vitro, noninduced B16 transfectants stimulated a specific IFN-gamma release response, but no cytolytic response (in a 4-h assay) in MHC class I-restricted CTL; in contrast, IFN-gamma-induced B16 targets were efficiently and specifically lysed by CTL. In vivo, B16 transfectants were specifically rejected by DNA-vaccinated syngeneic hosts through a T-dependent immune effector mechanism. The tumors showed evidence of massive apoptosis in vivo during the rejection process. The data suggest that CTL-derived IFN-gamma enhances an intrinsic suicide mechanism of these tumor cells in addition to facilitating lytic interactions of effectors with tumor targets.
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PMID:T cell-mediated, IFN-gamma-facilitated rejection of murine B16 melanomas. 967 Sep 68

As, the outcome of vaccine therapy was extremely heterogeneous in both human and murine hepatitis B virus (HBV)-carriers, the experiments presented here were performed to find out a prognostic marker of vaccine therapy using an animal model of HBV-carrier state, HBV-transgenic mice (Tg). Neither the prevaccinated titres of viral markers, such as hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) or HBV DNA, nor the function of lymphocytes prior to vaccination, had significant influence on the outcome of vaccine therapy. Two independent, placebo-controlled, trials of vaccine therapy for 12 months, one in 17 HBV-Tg and the other in 26 HBV-Tg (total, n=43) showed that the eight of 17 and 15 of 26 HBV-Tg that had potent dendritic cell (DC) function at the start of vaccine therapy became completely negative for HBsAg, HBeAg and reduced HBV DNA, whereas all 19 HBV-Tg that had poor DC function at the start of vaccine therapy became complete non-responders, although, the prevaccinated titres of HBsAg, and HBeAg were similar in all 43 HBV-Tg. Further study to find the mechanism underlying this revealed that there was up-regulation of major histocompatibility complex (MHC) class II, CD86 antigens on DC and increased production of interleukin-12 (IL-12) by DC and of IL-2, and tumour necrosis factor-alpha (TNF-alpha) in DC/T-cell cultures when vaccine containing HBsAg was injected in HBV-Tg with potent DC function but not in HBV-Tg with poor DC function. This is the first report on the prognostic importance of DC during an immune therapy. Degree of activation of DC following vaccination would possibly help to predict the outcome of vaccine therapy in human HBV-carriers. These data also provide the scientific and logical basis to up-regulate the function of the DC before an immune therapy.
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PMID:Prognostic importance of antigen-presenting dendritic cells during vaccine therapy in a murine hepatitis B virus carrier. 1023 83

Oligodeoxynucleotides (ODN) containing unmethylated CpG dinucleotides within specific sequence contexts (CpG motifs) are detected, like bacterial or viral DNA, as a danger signal by the vertebrate immune system. CpG ODN synthesized with a nuclease-resistant phosphorothioate backbone have been shown to be potent Th1-directed adjuvants in mice, but these motifs have been relatively inactive on primate leukocytes in vitro. Moreover, in vitro assays that predict in vivo adjuvant activity for primates have not been reported. In the present study we tested a panel of CpG ODN for their in vitro and in vivo immune effects in mice and identified in vitro activation of B and NK cells as excellent predictors of in vivo adjuvant activity. Therefore, we tested >250 phosphorothioate ODN for their capacity to stimulate proliferation and CD86 expression of human B cells and to induce lytic activity and CD69 expression of human NK cells. These studies revealed that the sequence, number, and spacing of individual CpG motifs contribute to the immunostimulatory activity of a CpG phosphorothioate ODN. An ODN with a TpC dinucleotide at the 5' end followed by three 6 mer CpG motifs (5'-GTCGTT-3') separated by TpT dinucleotides consistently showed the highest activity for human, chimpanzee, and rhesus monkey leukocytes. Chimpanzees or monkeys vaccinated once against hepatitis B with this CpG ODN adjuvant developed 15 times higher anti-hepatitis B Ab titers than those receiving vaccine alone. In conclusion, we report an optimal human CpG motif for phosphorothioate ODN that is a candidate human vaccine adjuvant.
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PMID:Delineation of a CpG phosphorothioate oligodeoxynucleotide for activating primate immune responses in vitro and in vivo. 1064 Jul 83

BACKGROUND/AIMS: The function and phenotype of antigen-presenting dendritic cells (DC) have been checked in patients with chronic hepatitis (CH) undergoing vaccine therapy to have insight about the mechanism of this immune therapy. SUBJECTS AND METHODS: Eleven patients with CH due to hepatitis B virus (HBV) were injected with vaccine containing 20 &mgr;g of hepatitis B surface antigen (HBsAg) once at every 2 weeks for 12 consecutive times. The serum interluekin-12 levels were estimated and the function and phenotype of peripheral blood DC were checked before, during and after the vaccine therapy. RESULTS: Sustained normalization of DNA-polymerase activity and alanine aminotransferase were seen in six patients (complete responders [CR]) due to vaccine therapy. The levels of serum interleukin-12 (P<0.01), the stimulatory capacity of peripheral blood DC (P<0.05) and the numbers of CD83-positive mature DC and CD86-positive activated DC (P<0.05) were significantly increased due to vaccination in CH-B patients, especially in younger patients. CONCLUSIONS: A role of DC during vaccine therapy is shown. This study also indicates that more effective vaccine therapy can be developed by upregulating the function of DC in situ in younger patients.
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PMID:Activation and maturation of antigen-presenting dendritic cells during vaccine therapy in patients with chronic hepatitis due to hepatitis B virus. 1208 54

Dendritic cell (DC) maturation is critical for the induction of antigen-specific T lymphocyte responses and may be essential for the development of human vaccines relying on T cell immunity. We investigated the effects on human DC of OM-197, a synthetic pseudodipeptide derived from amino acids, linked to three fatty acid chains and devoid of endotoxin properties. OM-197 upregulated the expression of HLA-DR, CD80, CD86, CD83, CD40 and CD54 at the surface of myeloid DC naturally present in blood as well as of DC generated in vitro from monocytes using IL-4 and GM-CSF. OM-197 also induced the release of IL-12 and TNF-alpha from DC. Finally, DC incubated with OM-197 after pulsing with hepatitis B surface antigen (HBs Ag) induced in vitro expansion of IFN-gamma-secreting HBs Ag-specific CD4(+) T lymphocytes from naive individuals. Taken together, these data identify OM-197 as a potential vaccine adjuvant for the induction of Th1-type responses.
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PMID:OM197-MP-AC induces the maturation of human dendritic cells and promotes a primary T cell response. 1263 19

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 Nef gene is a major determinant of HIV-1 pathogenicity. Several immunomodulatory functions have been reported for Nef, including down-regulation of CD4 and class I MHC in T-lymphocytes, and the ability to enhance viral transmission from macrophages and dendritic cells (DC) to T-lymphocytes. In this study, HIV-1 (SF2 strain) Nef was expressed in human monocyte-derived dendritic cells, using an adenovirus based delivery system. Nef expression resulted in decreased CD4 levels, but no change to class I MHC, and no impairment in the ability of DC to stimulate recall PPD responses, mixed leukocyte responses, or hepatitis B-specific CD8 responses. The adenovirus vector itself stimulated a strong recall CD4 response in all individuals tested, and also induced up-regulation of class I MHC, CD86 and CD40 on the dendritic cell surface. The study provides no evidence that HIV Nef impairs the function of human dendritic cells, and suggests that delivery of Nef to dendritic cells may be one strategy with which to stimulate an HIV-1 immune response.
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PMID:The functional consequences of delivery of HIV-1 Nef to dendritic cells using an adenoviral vector. 1467 Mar 36

Hepatitis B surface antigen (HBsAg)-pulsed murine spleen dendritic cells (DCs) have shown tremendous therapeutic potentials in chronic hepatitis B virus (HBV) carriers however, there has been no study regarding the feasibility of using HBsAg-pulsed DCs in human. Five human healthy volunteers with no apparent concomitant diseases were enrolled in this study. DCs were enriched from peripheral blood of each volunteer in endotoxin-free and sterilized conditions. HBsAg-pulsed DCs were prepared by culturing DCs with a commercial-available human grade vaccine containing HBsAg. After assessing the expression of HLA DR and CD86 on HBsAg-pulsed DCs, 5 million HBsAg-pulsed DCs were injected intradermally, once, to each volunteer. The volunteers were serially observed for safety and efficacy of administration of HBsAg-pulsed DCs. No evidence of physical, biochemical, and immunological abnormalities were documented in any volunteer during the next 28 days following administration of HBsAg-pulsed DCs. A single administration of HBsAg-pulsed DCs resulted in upregulation of anti-HBs in two anti-HBs(+) volunteers. Moreover, anti-HBs were detected in two anti-HBs(-) volunteer, 2 weeks after administration of HBsAg-pulsed DCs. This study provides the scientific and ethical basis for using HBsAg-pulsed DCs for therapeutic and prophylactic purposes in patients with chronic hepatitis B and non-responders to hepatitis B vaccine, respectively.
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PMID:Safety and efficacy of hepatitis B surface antigen-pulsed dendritic cells in human volunteers. 1520 76

Dendritic cells (DC) play an important role in the induction of T-cell responses. We hypothesize that the hampered antiviral T-cell response in chronic hepatitis B patients is a result of impaired dendritic cell function. In this study, we compared the number, phenotype and functionality of two important blood precursor DC, myeloid DC (mDC) and plasmacytoid DC (pDC), of chronic hepatitis B patients with healthy volunteers. No differences in percentages of mDC and pDC in peripheral blood mononuclear cells were observed between chronic hepatitis B patients and healthy controls. The allostimulatory capacity of isolated and in vitro matured mDC, but not of pDC, was significantly decreased in patients compared to controls. Accordingly, a decreased percentage of mDC expressing CD80 and CD86 was observed after maturation, compared to controls. In addition, mDC of patients showed a reduced capacity to produce tumor necrosis factor alpha after a stimulus with synthetic double-stranded RNA and interferon gamma. Purified pDC from patients produced less interferon alpha, an important antiviral cytokine, in response to stimulation with Staphylococcus aureus Cowan strain I than pDC isolated from controls. In conclusion, mDC and pDC are functionally impaired in patients with chronic hepatitis B. This might be an important way by which hepatitis B virus evades an adequate immune response, leading to viral persistence and disease chronicity.
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PMID:Functional impairment of myeloid and plasmacytoid dendritic cells of patients with chronic hepatitis B. 1534 14


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