Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The distribution and phenotypic characterization of T cell receptor (TCR) gamma delta cells in human liver tissue was investigated immunohistochemically at light and electron microscopic levels. In chronic liver disease, there was a significant increase in the number of TCR gamma delta cells and in the percentage of TCR gamma delta cells to CD3+ cells in the portal areas and hepatic sinusoids. Hepatic TCR gamma delta cells were classified as small or large gamma delta cells. Large gamma delta cells were increased in chronic liver disease, whereas both small and large gamma delta cells were increased in the portal areas and hepatic sinusoids in liver cirrhosis. The increased TCR gamma delta cells were of the BB3+ (peripheral) type, indicating that TCR gamma delta cells in the liver were of the same lineage as those in the peripheral blood. In addition, the majority of the TCR gamma delta cells in the portal areas of liver cirrhosis patients were CD4- and CD8- (double negative). Immunoelectron microscopy showed that the large gamma delta cells were lymphoblastoid and contained multivesicles. The present study clearly demonstrated that there are two types of TCR gamma delta cells, and that these cells were significantly increased in the livers of patients with chronic liver disease. This suggests that they may be involved in regulation of the immune response and hepatocellular damage in chronic liver disease.
 ...
PMID:Immunohistochemical study of T cell receptor gamma delta cells in chronic liver disease. 138 94

Approximately 5% of the world population is infected by the hepatitis B virus (HBV) that causes a necroinflammatory liver disease of variable duration and severity. Chronically infected patients with active liver disease carry a high risk of developing cirrhosis and hepatocellular carcinoma. The immune response to HBV-encoded antigens is responsible both for viral clearance and for disease pathogenesis during this infection. While the humoral antibody response to viral envelope antigens contributes to the clearance of circulating virus particles, the cellular immune response to the envelope, nucleocapsid, and polymerase antigens eliminates infected cells. The class I- and class II-restricted T cell responses to the virus are vigorous, polyclonal, and multispecific in acutely infected patients who successfully clear the virus, and the responses are relatively weak and more narrowly focused in chronically infected patients who do not. The pathogenetic and antiviral potential of the cytotoxic T lymphocyte (CTL) response to HBV has been demonstrated by the induction of a severe necroinflammatory liver disease following the adoptive transfer of HBsAg-specific CTL into HBV transgenic mice, and by the noncytolytic suppression of viral gene expression and replication in the same animals by a posttranscriptional mechanism mediated by interferon gamma, tumor necrosis factor alpha, and interleukin 2. The dominant cause of viral persistence during HBV infection is the development of a weak antiviral immune response to the viral antigens. While neonatal tolerance probably plays an important role in viral persistence in patients infected at birth, the basis for poor responsiveness in adult-onset infection is not well understood and requires further analysis. Viral evasion by epitope inactivation and T cell receptor antagonism may contribute to the worsening of viral persistence in the setting of an ineffective immune response, as can the incomplete downregulation of viral gene expression and the infection of immunologically privileged tissues. Chronic liver cell injury and the attendant inflammatory and regenerative responses create the mutagenic and mitogenic stimuli for the development of DNA damage that can cause hepatocellular carcinoma. Elucidation of the immunological and virological basis for HBV persistence may yield immunotherapeutic and antiviral strategies to terminate chronic HBV infection and reduce the risk of its life-threatening sequellae.
 ...
PMID:Hepatitis B virus immunopathogenesis. 761 25

The localization and distribution of gamma delta T cell receptor (TCR)-positive cells (gamma delta T cells) in hepatocellular carcinoma capsules was investigated immunohistochemically at both light and electron microscopic levels. Most of the mononuclear cells infiltrating the tumor capsules were CD3-positive. Together with gamma delta T cells, they were significantly increased in the tumor capsules compared to amounts in the fibrous septa in non-cancerous cirrhotic areas of the same liver, and compared to amounts in the liver of patients with cirrhosis. Phenotypic characterization by the two-color double-staining technique showed that CD8/gamma delta cells were significantly increased in the tumor capsule, and that more than one-third of gamma delta TCR-positive cells also expressed the CD56 antigen. Morphological observation revealed that large gamma delta T cells were increased in number in the tumor capsule and that the cytoplasm of these cells contained multivesicular bodies and dense granules. These morphological features were similar to those of large granular lymphocytes, and most of the gamma delta T cells were also positive for BB3. This suggests that extrathymic maturation of gamma delta T cells occurs in the tumor capsule, and that these gamma delta T cells may have a cytolytic effect on tumor cells, as shown in large granular lymphocytes; further, the results suggest that these cells may play a role in the defense against tumor expansion.
 ...
PMID:Immunohistochemical study of gamma delta T cell receptor-positive cells in the capsular region of hepatocellular carcinoma: possible role in defense against expansion of carcinoma in the liver. 764

Approximately 5% of the world population is infected by the hepatitis B virus (HBV) which causes a necroinflammatory liver disease of variable duration and severity. Chronically infected patients with active liver disease carry a high risk of developing cirrhosis and hepatocellular carcinoma. The immune response to HBV-encoded antigens is responsible both for viral clearance and for disease pathogenesis during this infection. While the humoral antibody response to viral envelope antigens contributes to the clearance of circulating virus particles, the cellular immune response to the envelope, nucleocapsid and polymerase antigens eliminates infected cells. The class I- and class II-restricted T cell responses to the virus are vigorous, polyclonal and multispecific in acutely infected patients who successfully clear the virus, and they are relatively weak and more narrowly focussed in chronically infected patients who do not. The pathogenetic and antiviral potential of the cytotoxic T lymphocyte (CTL) response to HBV have been demonstrated by the induction of a severe necroinflammatory liver disease following the adoptive transfer of HBV surface antigen-specific CTL into HBV transgenic mice, and by the noncytolytic suppression of viral gene expression and replication in the same animals by a post-transcriptional mechanism mediated by interferon-gamma, tumor necrosis factor-alpha and interleukin-2. The dominant cause of viral persistence during HBV infection is the development of a weak antiviral immune response to the viral antigens. While neonatal tolerance probably plays an important role in viral persistence in patients infected at birth, the basis for poor responsiveness in adult onset infection is not well understood and requires further analysis. Viral evasion by epitope inactivation and T cell receptor antagonism may contribute to the worsening of viral persistence in the setting of an ineffective immune response, as can the incomplete down-regulation of viral gene expression and the infection of immunologically privileged tissues. Chronic liver cell injury and the attendant inflammatory and regenerative responses create the mutagenic and mitogenic stimuli for the development of DNA damage that can cause hepatocellular carcinoma. Elucidation of the immunological and virological basis for HBV persistence may yield immunotherapeutic and antiviral strategies to terminate chronic HBV infection and reduce the risk of its life-threatening sequellae.
 ...
PMID:Hepatitis B virus immunopathology. 857 Nov 72

Idiopathic portal hypertension (IPH), so called Banti's disease, is characterized by anemia, splenomegaly and portal hypertension. While sharing certain clinical features, IPH is distinct from liver cirrhosis not only in histopathology and natural history but also in vascular anatomy and portal hemodynamics. Our studies have shown that the majority of patients with IPH have high serum levels of immunoglobulins, including autoantibodies, associated with abnormally high frequencies of activated T cells and the biased usage of particular T cell receptor (TCR) V beta gene segments. These results suggested that IPH was an immunological disorder mediated by a continuous stimulation with either a certain antigen or more likely a superantigen.
 ...
PMID:[The pathogenesis of idiopathic portal hypertension]. 886 18

Patients with cirrhosis of the liver frequently demonstrate anergy in intracutaneous tests and fail to respond to vaccination, suggesting impaired delayed hypersensitivity and other T cell-dependent functions in vivo. T cell activation through the coordinated interaction of different cells of the immune system (B cell, antigen-presenting cells (APC)) is an important step in the induction of cellular and humoral immune responses. Impaired T cell-dependent functions in patients with liver cirrhosis may thus be explained by defective T cell activation. We prospectively investigated T cell activation pathways in 12 patients (nine males, three females) with alcoholic liver cirrhosis (seven Child Pugh stage A and B (CP A + B), five Child Pugh stage C (CP C)) and five healthy controls and compared the in vitro results of T cell activation with data obtained in vivo, e.g. intracutaneous tests and vaccination against hepatitis B surface antigen (HBs-Ag). Five out of eight patients who completed vaccination against hepatitis B virus infection were non-responders; one of the three responders had a non-protective anti-HBs titre. Moreover, three of five patients with alcoholic liver cirrhosis CP A + B, and two out of three with CP C were anergic in intracutaneous tests to a set of diverse antigens. All parameters of T cell activation were normal, including proliferation mediated by CD2, CD3-T cell receptor (TCR) complex, and CD28; acquisition of responsiveness to exogenous IL-2 and IL-4; activation of proteinkinase C (PKC) by phorbol ester and calcium influx by addition of ionomycin. The ability of monocytes to deliver costimulatory signals was preserved in patients with alcoholic cirrhosis. In addition, serum of patients with alcoholic liver disease did not inhibit T cell proliferation. We conclude that, although in patients with alcoholic liver cirrhosis T cell-dependent functions are impaired in vivo, T cell activation pathways are not responsible for the observed immune defect.
 ...
PMID:Analysis of T cell activation pathways in patients with liver cirrhosis, impaired delayed hypersensitivity and other T cell-dependent functions. 909 23

HIV and hepatis C virus (HCV) coinfection is frequently associated with rapid progression of HCV-related disease, resulting in a higher risk of cirrhosis. Data suggest that natural T cells expressing the Vdelta1 T cell receptor rearrangement are recruited in the liver of chronically HCV-infected patients and are increased in the peripheral blood of HIV-infected persons. We studied gammadelta T cell distribution in the peripheral blood and liver of HCV-infected and HIV/HCV-coinfected patients in the presence and absence of antiretroviral therapy. We observed that Vdelta1+ T cells releasing helper T cell type 1 cytokines are compartmentalized not only in the liver of HCV+ patients, but also of HIV/HCV-coinfected persons. HIV/HCV patients showed an increased frequency of both peripheral and intrahepatic Vdelta1 natural T lymphocytes, resulting in a higher degree of hepatic inflammation when compared with patients with other liver diseases. Finally, highly active antiretroviral therapy (HAART) was unable to restore Vdelta1T cell circulation to normal levels in chronically HIV-infected persons. We conclude that gammadelta T lymphocytes released from tissue to the bloodstream circulation under the influence of chronic HIV infection may contribute to intrahepatic Vdelta1 compartmentalization and progression of liver disease, independently of HAART.
 ...
PMID:Gammadelta T cell activation by chronic HIV infection may contribute to intrahepatic vdelta1 compartmentalization and hepatitis C virus disease progression independent of highly active antiretroviral therapy. 1160 46

Hepatitis C virus (HCV) infection induces an acute and chronic liver inflammation through an immune-mediated pathway that may lead to cirrhosis and liver failure. Indeed, HCV-related hepatitis is characterized by a dramatic lymphocyte infiltrate into the liver which is mainly composed by HCV non-specific cells. Several data indicated that interferon (IFN)-gamma secretion by intrahepatic lymphocytes (IHL) may drive non-specific cell homing to the liver, inducing interferon inducible protein-10 (IP-10) production. An interesting hallmark of these IHL is the recruitment of lymphocytes associated with mechanisms of innate immunity, such as natural killer (NK), natural killer T (NKT) and gamma delta T lymphocytes. CD81 triggering on NK cell surface by the HCV envelope glycoprotein E2 was recently shown to inhibit NK cell function in the liver of HCV-infected persons, resulting in a possible mechanism contributing to the lack of virus clearance and to the establishment of chronic infection. In contrast, intrahepatic NKT cells restricted to CD1d molecules expressed on the hepatocyte surface may contribute to a large extent to liver damage. Finally, an increased frequency of T cells expressing the gamma delta T cell receptor (TCR) was observed in HCV-infected liver and recent observations indicate that intrahepatic gamma delta T cell activation could be directly induced by the HCV/E2 particle through CD81 triggering. These cells are not HCV specific, are able to kill target cells including primary hepatocytes and their ability to produce T helper (Th)1 cytokines is associated with a higher degree of liver disease. Together, CD1d/NKT and/or E2/CD81 interactions may play a major role in the establishment of HCV immunopathogenesis. In the absence of virus clearance, the chemokine-driven recruitment of lymphocytes with an innate cytotoxic behavior in the liver of HCV-infected patients may boost itself, leading to necroinflammatory and fibrotic liver disease.
 ...
PMID:Lymphocyte distribution and intrahepatic compartmentalization during HCV infection: a main role for MHC-unrestricted T cells. 1245 64

IL-18 is a pleiotropic cytokine and is produced by various types of cells including activated macrophages, particularly Kupffer cells. IL-18 has potential to activate inflammatory responses through induction of IFN-gamma production in collaboration with IL-12. Somewhat paradoxically, IL-18 also has the capacity to induce allergic responses via induction of IL-4 production by T helper cells and to activate mast cells and basophils to release atopic effector molecules such as histamine. Indeed, IL-18 is involved in inflammatory tissue injuries, such as Crohn's disease and atherosclerosis, and also in hyper IgE and atopic dermatitis. IL-18 is particularly important for induction of experimental liver diseases. Endotoxin-induced liver injury or Fas ligand-induced hepatitis is caused by endogenous IL-18 in mice. Moreover, patients with liver diseases such as fulminant hepatitis, liver cirrhosis due to hepatitis virus infection and primary biliary cirrhosis show elevation of serum levels of IL-18, that correlates with the corresponding disease severity. Therefore, endogenous IL-18 plays a major role in induction of some types of liver injuries in mice and human. NKT cells that express both T cell receptor and NK cell marker are abundant in the liver of mice and human. Recent studies have revealed that NKT cells participate in some types of liver injuries, such as concanavalin A-induced T cell-mediated hepatitis and malaria hepatitis. In this review article, we focus on IL-18-involving liver damages and NKT-cell-mediated liver injuries.
 ...
PMID:Cytokine-induced inflammatory liver injuries. 1452 86

Hepatitis C virus (HCV) has been reported to elicit B and T cell immunity in infected patients. Despite the presence of antiviral immunity, many patients develop chronic infections leading to cirrhosis, hepatocellular carcinoma, and liver failure that can require transplantation. We have previously described the presence of HLA-A2-restricted, HCV NS3-reactive cytotoxic T lymphocytes (CTL) in the blood of HLA-A2- liver transplantation patients that received an HLA-A2+ liver allograft. These T cells are analogous to the "allospecific" T cells that have been described in hematopoietic stem cell transplantation patients. It has been speculated that allospecific T cells express high-affinity T cell receptors (TCRs). To determine if our HCV-reactive T cells expressed TCRs with relatively high affinity for antigen, we identified and cloned a TCR from an allospecific HLA-A2-restricted, HCV:NS3:1406-1415-reactive CD8+ T cell clone and expressed this HCV TCR in Jurkat cells. Tetramer binding to HCV TCR-transduced Jurkat cells required CD8 expression, whereas antigen recognition did not. In conclusion, based on the reactivity of the TCR-transduced Jurkat cells, we have identified a TCR that transfers anti-HCV reactivity to alternate effectors. These data suggest this high affinity HCV-specific TCR might have potential new immunotherapic implications.
 ...
PMID:Identification of a hepatitis C virus-reactive T cell receptor that does not require CD8 for target cell recognition. 1662 27


1 2 Next >>