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

The cellular basis for the variation in induction of monocyte procoagulant activity (PCA) by murine hepatitis virus strain 3 (MHV-3) was examined using a set of recombinant inbred strains of mice derived from the resistant (A/J) and susceptible C57B1/6J (B) progenitors. Induction of PCA by MHV-3 required live virus and host protein and RNA synthesis. Absolute restriction for induction of PCA was observed at the level of the macrophage. Peritoneal macrophages from resistant parental A/J and RI strains (AXB5) could not be induced to express PCA when stimulated by MHV-3 alone or in the presence of lymphocytes from susceptible and H-2 compatible RI mice (AXB3) although they did respond to endotoxin (LPS). In contrast, macrophages from both susceptible (AXB3) and semisusceptible (AXB1) RI strains of mice expressed a similar increase in PCA after stimulation with MHV-3 in the absence of lymphocytes. The levels of PCA expressed by macrophages in the presence of Thy-1.2+ lymphocytes correlated with susceptibility to disease. Thy-1.2+ lymphocytes from susceptible RI AXB3 mice could induce levels of PCA in macrophages from semisusceptible RI AXB1 mice equivalent to that seen in cultures of macrophages and lymphocytes from susceptible mice. Further subfractionation of Thy-1.2+ cells demonstrated that L3T4+ cells instructed macrophages to produce PCA. Thy-1.2+ cells from MHV-3 immunized resistant AXB5 mice, but not from non-immunized mice, were able to suppress induction of PCA. This suppressor cell activity could be detected 4 days after immunization, reaching maximal activity at day 7 with significant suppression even at 28 days. The PCA was shown to have direct prothrombin cleaving activity (prothrombinase) by ELISA and immunofluorescence staining using the mAb 3D4.3. These results demonstrate that induction of a unique PCA (prothrombinase) is restricted at the level of the macrophage and define a regulatory role for T lymphocytes in its induction.
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PMID:Cellular and metabolic requirements for induction of macrophage procoagulant activity by murine hepatitis virus strain 3 in vitro. 170 94

Progressive hepatitis in athymic nude (nu/nu) mice due to a low-virulent mouse hepatitis virus, MHV-2 cc, was examined for involvement of immunocytes and serum antibodies. At 3 to 6 weeks postinoculation (p.i.) a considerable number of Mac 1- and asialo GM1-positive cells were accumulated in the affected liver and spleen. There were also some Thy-1-positive cells. Later than 2 weeks p.i., serum IgG and IgM antibodies were detected in parallel with virus-neutralizing activity, while the IgG levels were lower than those of infected euthymic (nu/+) littermates. By transfer of the infected nu/nu mouse serum, the recipient euthymic mice acquired resistance to lethal challenge infection with a virulent virus, MHV-2.
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PMID:Immunopathology of chronic progressive hepatitis in nude mice infected with low-virulent mouse hepatitis virus. 255 Jul 46

The effector cell in mouse spleen which mediates natural cytotoxicity against mouse hepatitis virus (MHV)-infected target cells was characterized. The target cells were MHV-infected BALB/c 3T3, and the assay time was 3 hr. The effector cell, designated virus killer (VK) cell for the purpose of discussion, had the following phenotype: lymphocyte morphology, plastic-nonadherent, nylon wool-adherent, nonphagocytic, cyclophosphamide-sensitive; by antibody plus complement (C) depletion studies, it was asialo GM1-, NK 1.2 alloantigen-negative, Thy-1.2-, Lyt-5-, and macrophage antigen-negative; by rosetting techniques, it was Fc receptor-positive and surface Fab+; by flow cytometry (FACS) analysis, it was Lyt-2-, MAC-1-, Ia+, IgG (gamma)+, IgM (mu)+, IgD (delta)+, and B cell lineage antibody B-220+. NK cells, measured for cytotoxicity on YAC-1 cells, were similarly tested and were found to differ from the VK cell in the following properties: nylon wool-nonadherent, asialo GM1+, NK alloantigen-positive, Lyt-5+, surface Fab-, MAC-1+, Ia-, IgG-, IgM-, IgD-, and B-220-. The VK effector cell had a phenotype highly distinguishable from NK cells, effectors most commonly associated with antiviral natural cytotoxicity. The VK cell had a phenotype identical to that of a B lymphocyte and was identified as such. Although the effector cells displayed cell surface antibody, the antibody did not appear to be involved in lysis, because lysis could not be blocked by F(ab)'2 directed against Fab, mu, or delta. Cytotoxicity was more likely associated with recognition of the B lymphocyte surface by the MHV glycoprotein E2, as shown in the accompanying companion paper. This is the first demonstration that natural cytotoxicity can be mediated by B lymphocytes.
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PMID:Natural cytotoxicity against mouse hepatitis virus-infected cells. II. A cytotoxic effector cell with a B lymphocyte phenotype. 300 99

A model for monitoring the accumulation of natural killer cell/large granular lymphocytes (NK/LGL) at a site of virus replication was studied by using mice infected i.p. with either lymphocytic choriomeningitis virus (LCMV), murine cytomegalovirus (MCMV), mouse hepatitis virus (MHV), Pichinde virus, or vaccinia virus. An i.p. but not i.v. infection resulted in a localized increase in NK/LGL cell number (a fourfold to greater than 20-fold increase) and augmentation (a 10- to 20-fold increase) of NK cell activity associated with virus-induced peritoneal exudate cell (PEC) populations. An increase in NK/LGL cell number was detected as early as 12 hr postinfection (p.i.) and peaked at 3 days p.i. with MHV. The initial LGL recruited into the peritoneal cavity at 1 to 3 days p.i. were nonadherent to plastic and were demonstrated to have an NK cell phenotype: asialo GM1+, Thy-1.2 +/-, Lyt-2.2-, and J11d-. The peak number of LGL appeared at 7 days after infection with the NK cell-resistant virus, LCMV. This LGL population had been previously demonstrated to contain cytotoxic T lymphocyte/LGL (CTL/LGL) as well as NK/LGL. During an MHV infection the number of LGL decreased between days 3 and 7 p.i., suggesting that the second wave of CTL/LGL was absent. These findings may explain the absence of a good MHV-CTL model. Virus-induced, activated NK/LGL responded to chemotactic signals by migrating in a unidirectional manner across two 5-microns pore size polycarbonate filters during 7 hr in vitro chemotaxis assays. Wash-out fluid obtained from the peritoneal cavity contained chemotactic activity for NK/LGL as well as for other cell types. We conclude that production and/or release of chemotactic factors at sites of virus replication are at least partially responsible for the accumulation of NK/LGL at these sites.
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PMID:Accumulation and chemotaxis of natural killer/large granular lymphocytes at sites of virus replication. 302 67

A model for immunologically T cell-mediated hepatitis was established in mice infected with lymphocytic choriomeningitis virus (LCMV). The severity of hepatitis was monitored histologically and by determination of changes in serum levels of the enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamate dehydrogenase (GLDH), and alkaline phosphatase (AP). Kinetics of histological disease manifestations, increases of liver enzyme levels in the serum, and cytotoxic T cell activities in livers and spleens all correlated and were dependent upon several parameters: LCMV-isolate; LCMV-WE caused extensive hepatitis, LCMV-Armstrong virtually none. Virus dose. Route of infection; i.v. or i.p. infection caused hepatitis, whereas infection into the footpad did not. The general genetic background of the murine host; of the strains tested, Swiss mice and A-strain mice were more susceptible than C57BL or CBA mice; BALB/c and DBA/2 mice were least susceptible. The degree of immunocompetence of the murine host; T cell deficient nu/nu mice never developed hepatitis, whereas nu/+ or +/+ mice always did. B cell-depleted anti-IgM-treated mice developed immune-mediated hepatitis comparably or even more extensively than control mice. Local cytotoxic T cell activity; mononuclear cells isolated from livers during the period of overt hepatitis were two to five times more active than equal numbers of spleen cells. Adoptive transfer of nylon wool-nonadherent anti-Thy-1.2 and anti-Lyt-2 plus C-sensitive, anti-L3T4 plus C-resistant lymphocytes into irradiated mice preinfected with LCMV-WE caused a rapid time- and dose-dependent linear increase of serum enzyme levels. This increase was caused by adoptive transfer of lymphocytes if immune cell donors and recipient mice shared class I, but not when they shared class II histocompatibility antigens. The donor cell dose-dependent increase of these enzymes was first measurable 6-18 h after transfer with 2 X 10(8) cells or 3 X 10(6) cells, respectively. The time-dependent increase caused by the adoptive transfer of 1-2 X 10(8) cells was strictly linear during a period of up to 25-40 h. These results indicate single-hit kinetics of liver cell death and suggest that effector T cells destroy infected liver cells via direct contact rather than via soluble toxic mediators. The results may represent the best in vivo correlate of the in vitro 51Cr-release assay that has been analyzed so far, and strongly support the view that antiviral cytotoxic T cells are directly cytolytic in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:T cell-mediated hepatitis in mice infected with lymphocytic choriomeningitis virus. Liver cell destruction by H-2 class I-restricted virus-specific cytotoxic T cells as a physiological correlate of the 51Cr-release assay? 348 5

Experimental autoimmune hepatitis was induced in B10.A(5R) mice sensitized by repeated intramuscular injections of syngeneic liver antigens emulsified with complete Freund's adjuvant. A 300R X-irradiation followed by two more injections after the sixth intramuscular sensitization to the mice resulted in active hepatitis with severe piecemeal necrosis. An intravenous adoptive transfer of spleen cells from the sensitized mice into normal syngeneic mice caused hepatitis in recipients which was characterized by extensive focal hepatic cell necrosis in the lobules. The transfer of spleen cells treated with monoclonal anti-Thy-1.2 antibody plus complement failed to induce hepatitis, while the transfer of T cell-enriched spleen cells by the panning method using rabbit anti-mouse immunoglobulin-coated dishes caused a somewhat more severe hepatitis than that caused by the transfer of whole spleen cells of the sensitized mice.
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PMID:Studies on the pathogenesis of murine experimental autoimmune active hepatitis: sensitized T cell involvement in its induction. 349 95

Resistance of SJL/J mice to intracranial inoculation with the JHM strain of mouse hepatitis, a coronavirus, is dependent upon the age of the animals at inoculation. Animals 12 weeks of age or older are resistant, whereas those 6 weeks or younger are uniformly susceptible to viral infection. Spleen cells or thioglycolate elicited peritoneal exudate cells can transfer resistance from 12-week-old to 6-week-old recipients. Removal of the adherent cells from either spleen or peritoneal cells ablated protection. Adherent cells from 12-week-old mice were protective even after depletion of Ia- and Thy-1-bearing cells. Antiviral antibody, thioglycolate injection into 6-week-old animals, and nylon wool-purified T cells were ineffective in mediating resistance. Adherent cells transferred 4 days before virus challenge, but not after challenge, were protective. Thus, there is an age-related change in SJL mice that protects from acute central nervous system disease, which may be due to maturation of a specialized adherent cell population.
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PMID:Resistance to fatal central nervous system disease by mouse hepatitis virus, strain JHM. II. Adherent cell-mediated protection. 624 28

Peritoneal exudate cells from strains of mice both resistant and susceptible to challenge with mouse hepatitis virus strain JHM were examined for extrinsic and intrinsic antiviral activity. Thioglycolate-elicited and resident peritoneal cells from uninfected mice were able to suppress viral growth in a permissive cell. The active cell in both populations is an adherent, radiation-resistant, Thy-1.2 antigen- and Ia antigen-negative cell. The suppression of virus replication was not related to nonspecific cellular cytotoxicity directed against the permissive host cell, and no interferon was detected. The expression of extrinsic antiviral activity was not related to the ability of the host to resist mouse hepatitis virus infection by virtue of either age or genetic background. The expression of intrinsic antiviral activity, on the other hand, correlated with the ability of the host to resist virus challenge, indicating a characteristic distinction between these two in vitro mechanisms of macrophage-mediated antiviral activity with regard to host resistance to viral infection. Further, the ability of a macrophage to support viral replication itself was independent of the ability of the macrophage to suppress virus growth in another cell.
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PMID:Macrophage antiviral activity: extrinsic versus intrinsic activity. 628 56

An in vivo murine model for immunodeficiency of both B and T cells is produced by continuous intraperitoneal infusion of 2'-deoxycoformycin (DCF), a specific tightly binding inhibitor of adenosine deaminase (ADase; adenosine aminohydrolase, EC 3.5.4.4). After DCF infusion, ADase of thymus, spleen, and lymph nodes was inhibited to varying degrees ranging from 57% to 100%. Immunodeficiency under these conditions was indicated by: (i) a striking decrease in lymphocyte response to the T-cell mitogens concanavalin A and phytohemagglutinin; (ii) an impairment of delayed hypersensitivity measured by the footpad reaction; (iii) a decrease in antibody production measured in both in vivo and in vitro plaque-forming cell assay; (iv) a significant prolongation of mouse skin allograft survival after transplantation into the C57BL/6J (H-2b) strain of skin from BALB/c (H-2d) mice; and (v) a marked lymphopenia. Histological examination indicated lymphoid degeneration in the thymus, lymph nodes, and spleen with no alterations in other tissues including bone marrow, kidney, lung, gastrointestinal tract, and liver except for the occurrence of hepatitis. A decrease in the number of Thy-1-positive cells in both spleen and lymph nodes further supported the fact of cytotoxicity of DCF to T cells. Anorexia and weight loss were observed within 5 days of continuous DCF infusion at 0.4 mg/kg body weight per day. These data indicate that this method provides an experimental model for future studies on the biochemical mechanisms responsible for the genetically determined severe combined immunodeficiency disease in man.
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PMID:Animal model for immune dysfunction associated with adenosine deaminase deficiency. 696 8

Severe combined immune deficient (SCID) mice infected orally with reovirus type 1/L die of hepatitis. Leukocytes bearing the cell surface antigens Thy-1.2 and asialoGM-1 (AsGM1) accumulate in the livers of infected animals. These cells display lytic activity toward natural killer-sensitive (YAC-1) and -resistant (P815) cell lines and murine hepatoma line Hepa 1/A1. Although these cells have the capacity to lyse infected hepatoma targets, they cannot clear the virus.
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PMID:Characterization of cytotoxic cells from reovirus-infected SCID mice: activated cells express natural killer- and lymphokine-activated killer-like activity but fail to clear infection. 774 45


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