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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Infection of mixed glial cell cultures with mouse hepatitis virus (MHV)-A59 results in an approximately six-fold increase in the level of major histocompatibility complex (MHC) class I mRNA. In situ hybridization of glial cell cultures infected with MHV-A59 again showed enhanced MHC mRNA expression, both in infected and uninfected cells. These results extend our earlier finding that MHC surface antigens are enhanced on astrocytes and oligodendrocytes after MHV-A59 infection and suggest that this enhancement is a result of an increase in the steady-state level of MHC mRNA. We further demonstrate that increases in MHC mRNA occur in the murine central nervous system (CNS) following infection in vivo. Northern blot analysis of RNA from the brains of infected animals showed transient expression of both MHC class I and class II mRNA over the first 14 days of infection. Expression coincided with viral replication and clearance. In situ hybridization of brain sections from infected animals showed that class I and class II expression was widespread throughout all portions of the brain and in uninfected as well as infected cells. Viral RNA, in contrast, was observed in small foci of cells and mostly within the limbic system. Thus enhancement of MHC mRNA was not restricted either to areas of infection or inflammation. The spatial relationship between viral and MHC expression supports our hypothesis that a soluble mediator is involved in the mechanism of the increase in MHC levels. The fact that MHC induction occurs in vivo as well as in vitro suggests MHC may be important in the mechanism of MHV-induced disease.
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PMID:Mouse hepatitis virus A59 increases steady-state levels of MHC mRNAs in primary glial cell cultures and in the murine central nervous system. 133 98

Intrahepatic infiltrate from 18 patients who died of fulminant hepatitis, was analyzed by an immunohistochemical method using formalin-fixed, paraffin-embedded liver sections and monoclonal antibodies. Inflammatory cells were characteristically located in the portal and periportal areas adjoining resting hepatocytes, but were infrequently found in the perivenular areas where hemorrhagic hepatocyte necrosis predominated. In the inflammatory infiltrate, T cells were the most predominant cell type, composing about two-thirds of the total hepatic infiltrate, followed by lysozyme-positive macrophages which composed about one-third of the total hepatic infiltrate, irrespective of the etiology of the fulminant hepatitis. On the other hand, B cells made up less than 2% in all cases, and plasma cells were also few, less than 2% in 12 of 18 cases. Furthermore, an enhanced display of beta 2-microglobulin on hepatocyte membranes was demonstrated in all cases with remaining hepatocytes, indicating an increased expression of class I MHC antigens on these cells. These results suggest that T cells may play an important role in the pathogenesis of the portal and periportal lesions of fulminant hepatitis, probably with a help of MHC class I antigens on hepatocytes, while hemorrhagic necrosis of hepatocytes around the central veins may be caused by a different mechanism, most likely a circulatory disturbance secondary to cell-mediated immune reactions in the periportal areas.
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PMID:The cellular infiltrate in the liver of patients with fulminant hepatitis: analysis of paraffin-embedded tissue sections. 160 Feb 59

CD4+ T cell lines specific for murine hepatitis virus (MHV) - JHM or myelin basic protein (MBP) proliferated when cultured together with MHC class I and II positive syngeneic rat astrocytes and either inactivated virus or MBP as antigen. The magnitude of the T cell proliferative response was comparable to that seen when thymocytes were used as a source of antigen presenting cells (APC). In contrast, MHC class I and II positive astrocytes were unable to significantly stimulate the proliferation of highly purified populations of naive CD4+ and CD8+ T cells in an allogeneic mixed lymphocyte reaction (MLR). Both T cell populations proliferated when mixed with allogeneic lymph node cells. Infection of the astrocytes with a variant of MHV-JHM (PI-AS22D) did not alter this cells incapacity to stimulate the naive CD4+ and CD8+ T cells to proliferate.
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PMID:Astrocytes as antigen presenting cells for primary and secondary T cell responses: effect of astrocyte infection by murine hepatitis virus. 196 61

Mice infected with the neurotropic JHM strain of mouse hepatitis virus (MHV-JHM) develop a demyelinating encephalomyelitis several weeks after infection. Astrogliosis and infiltration of inflammatory cells are prominent findings in the brains and spinal cords of infected mice. In this report, astrocytes in infected spinal cords were analyzed for expression of three pleiotropic cytokines, TNF-alpha, IL-1 beta, and IL-6; Type 2 nitric oxide synthase (iNOS); and MHC class I and II antigen. The data show that all three cytokines and iNOS are expressed by astrocytes in chronically infected spinal cords. These activated astrocytes are localized to areas of virus infection and demyelination, although most of the astrocytes expressing these proteins are not MHV-infected. MHC class I and II antigen can be detected in these spinal cords as well, but not in cells with the typical morphology of astrocytes. TNF-alpha, IL-6, and iNOS are also evident in the brains of mice with MHV-induced acute encephalitis, but in marked contrast to the results obtained with the chronically infected mice, most of the cells expressing these cytokines or iNOS had the morphology of macrophages or other mononuclear cells and very few appeared to be astrocytes. Additionally, astrocytes and, most likely, oligodendrocytes are infected in the spinal cords of mice with chronic demyelination. These results are consistent with a role for both viral infection of glial cells and high localized levels of proinflammatory cytokines and nitric oxide in the demyelinating process in mice infected with MHV-JHM. They also show that analogously to the human demyelinating disease, multiple sclerosis, astrocytes are a major cellular source for these cytokines in mice with chronic, but not acute disease.
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PMID:Activation of astrocytes in the spinal cord of mice chronically infected with a neurotropic coronavirus. 749 73

CD8+ T cells with cytotoxic activity against the surface glycoprotein (S) of mouse hepatitis virus, strain JHM, have been identified in the central nervous system (CNS) of both acutely and chronically infected C57BL/6 mice. In this report, two specific epitopes recognized by these CNS-derived cells were identified, using a panel of peptides chosen because they conformed to the allele-specific binding motif for MHC class I H-2Kb and H-2Db. The active peptides encompassed residues 510 to 518 (CSLWNGPHL, H-2Db) and 598 to 605 (RCQIFANI, H-2Kb). Both epitopes are located within the region of the S protein previously shown to be prone to deletion after passage in animals. These deleted strains are generally less neurovirulent than the wild-type virus but still are able to cause demyelination. Since C57BL/6 mice become persistently infected more commonly than many other strains of mice, these data are consistent with a role for CD8+ T-cell escape mutants in the pathogenesis of the demyelinating disease. This is the first report of CD8+ T-cell epitope localization within the S protein, the protein most strongly implicated thus far in pathogenesis in the host.
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PMID:CD8+ T-cell epitopes within the surface glycoprotein of a neurotropic coronavirus and correlation with pathogenicity. 749 35

Nonobese diabetic (NOD) mice and beta 2-microglobulin-gene-ablated mice (beta 2M -/-) show impaired presentation of major histocompatibility complex (MHC) class I and self-peptides, structures now recognized as critical for T-cell education to endogenous peptides. The naturally occurring NOD class I presentation abnormality appears to be attributable to, in part, a quantitative defect in the production of Tap-1 mRNA; Tap-1 with Tap-2 normally functions as a transporter for stable self-peptide and class I assembly. This study attempts to reverse NOD and beta 2-M -/- mouse autoreactivity by introduced or reestablished syngeneic class I presentation. Introduction of MHC class I and self-peptides on syngeneic MHC class I-matched cells specifically prevented diabetes in NOD mice and eliminated in vitro class I-directed T-cell autoreactivity in NOD and beta 2M -/- mice. Reestablishment of endogenous class I and self-peptide presentation in NOD mice was achieved with two well-described cures for the NOD mouse, complete Freund's adjuvant and mouse hepatitis virus. Both treatments induced Tap-1 mRNA, reestablished class I presentation of endogenous antigens, and eliminated in vitro and in vivo T-cell autoreactivity of self-peptides in the class I groove. These results substantiate a therapeutic role of self-peptide complexed with class I for T-cell education and suggest that some well-described NOD treatments may work, in part, through reestablishment of tolerance through class I and self-peptide.
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PMID:Elimination of self-peptide major histocompatibility complex class I reactivity in NOD and beta 2-microglobulin-negative mice. 765 37

Coronavirus-induced acute hepatitis is a complex event and the role of different components of the immune system with regard to defined viral proteins and the course of the infection is not yet clear. We have analysed the cytotoxic T-lymphocyte (CTL) response in mouse hepatitis virus (MHV-A59) infection. Surprisingly, we detected only a very clear virus-specific major histocompatibility complex (MHC) class II-restricted cytotoxicity in mice infected with MHV-A59. We found no evidence of activation of the classical CD8+ MHC class I-restricted CTL. The virus-specific CD4+ CTL derived from two different mouse strains having different MHC haplotypes recognized the same immunodominant epitope. This epitope, comprising the amino acid residues 329-343 of the viral S-glycoprotein, was recognized both at the polyclonal level and by virus-specific CTL clones. Transfer studies using a MHV-A59-specific CD4+ CTL clone showed significant protection against a lethal challenge with MHV-A59, implicating that these CD4+ CTL play a pivotal role in the protection against MHV-A59 infections.
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PMID:Predominance of MHC class II-restricted CD4+ cytotoxic T cells against mouse hepatitis virus A59. 779 24

Neurotropic strains of mouse hepatitis viruses (MHV) such as MHV-A59 (A59) and MHV-4 (JHMV) cause acute and chronic encephalomyelitis and demyelination in susceptible strains of mice and rats. They are widely used as models of human demyelinating diseases such as multiple sclerosis (MS), in which immune mechanisms are thought to participate in the development of lesions in the central nervous system (CNS). The effects of MHV infection on target cell functions in the CNS are not well understood, but A59 has been shown to induce the expression of MHC class I molecules in glial cells after in vivo and in vitro infection. Changes in class I expression in infected cells may contribute to the immunopathogenesis of MHV infection in the CNS. In this communication, a large panel of MHV strains was tested for their ability to stimulate class I expression in primary astrocytes in vitro. The data show that the more hepatotropic strains, such as MHV-A59, MHV-1, MHV-2, MHV-3, MHV-D, MHV-K, and MHV-NuU, were potent inducers of class I expression in astrocytes during acute infection, measured by radioimmunoassay. The Kb molecule was preferentially expressed over Db. By contrast, JHMV and several viral strains derived from it did not stimulate the expression of class I molecules. Assays of virus infectivity indicated that the class I-inducing activity did not correlate with the ability of the individual viral strain to replicate in astrocytes. However, exposure of the viruses or the supernatants from infected astrocytes to ultraviolet light abolished the class I-inducing activity, indicating that infectious virus is required for class I expression. These data also suggest that class I expression was induced directly by virus infection, and not by the secretion of a soluble substance into the medium by infected astrocytes. Finally, analyses of A59/JHMV recombinant viral strains suggest that class I-inducing activity resides in one of the A59 structural genes.
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PMID:Coronavirus induction of class I major histocompatibility complex expression in murine astrocytes is virus strain specific. 806 22

The genetic background of autoimmune diseases becomes more and more evident. Immunogenetics comprises the analysis of genes and their products located at the region 6p21 on the short arm of chromosome 6, which is also known as the major histocompatibility complex (MHC). MHC class I and II genes are highly polymorphic. The complement genes C2, C4A, C4B, and BF, which are also polymorphic, became known as MHC class III genes. In autoimmune hepatitis type 1, there is a dual association for white persons with either HLA-A1-B8-DR3 or HLA-DR4. In patients from Japan, autoimmune hepatitis type 1 is predominantly associated with HLA-DR4. This dual association is confirmed at the DNA level. Whereas only limited data are available for autoimmune hepatitis type 2, the association of primary biliary cirrhosis with HLA-DR8 is based on several studies. Primary sclerosing cholangitis is associated with HLA-B8-DR3 and -DR52a. This association was confirmed at the DNA level because of a significant increase of the DRB3*0101 allele. For DRB3*0101-negative individuals, a second association with DRB5*0101 (= DR2) was described. Further analysis of the hypervariable region of the HLA class II molecule indicates that lysine at position 71 is crucial for autoimmune hepatitis type 1 in white persons, whereas position 13 is important for people from Japan. In contrast, leucine at position 35 is important for patients with primary biliary cirrhosis, whereas leucine at position 38 is an important risk factor for primary sclerosing cholangitis. The MHC class III allele C4A-QO is significantly increased in autoimmune hepatitis type 1 and 2 and in primary biliary cirrhosis. Advances in immunogenetics will certainly increase our knowledge of the etiology and pathogenesis of immune-mediated liver diseases, which hopefully will lead to more specific therapeutic interventions.
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PMID:Immunogenetics of chronic liver diseases. 819 17

Cytotoxic T lymphocyte (CTL) activity specific for mouse hepatitis virus (MHV) JHM strain (JHMV or MHV-4) was examined using in vitro stimulated spleen cells derived from immunized C57BL/6 (H-2b) mice. Target cells infected with JHMV were specifically recognized; however, analysis of target cells expressing the virus structural proteins via recombinant vaccinia viruses showed no recognition of the viral nucleocapsid (N), membrane (M), small membrane (sM) or haemagglutinin-esterase (HE) proteins. Only target cells expressing the virus spike (S) protein were recognized. Furthermore, the majority of CTL activity was restricted to target cells expressing the MHC class I Db molecules. Analysis of truncations and deletions of the S protein expressed by recombinant vaccinia viruses and peptide coated targets identified a single antigenic epitope, aa 510-518, conforming to the Db binding motif. These amino acids are contained within a domain deleted from a number of strains of mouse hepatitis virus, suggesting a role for immune pressure. To determine the potential for CTL specific for an epitope(s) within a non-structural protein, 24 CTL lines were established and characterized. No evidence for the induction of non-specific CTL activity or virus-specific CTL restricted to an epitope in a non-structural protein was obtained. These data indicate that the predominant CTL activity in JHMV-infected C57BL/6 mice is Db restricted and specific for a single epitope contained within aa 510-518 of the S protein.
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PMID:The JHM strain of mouse hepatitis virus induces a spike protein-specific Db-restricted cytotoxic T cell response. 862 36


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