Abstract:
:Liver fibrosis is commonly observed in chronic liver disease. However, the immunological mechanisms underlying hepatic fibrosis due to chronic inflammation are not well defined, mainly because suitable experimental models have not been established. We have found that weekly i.v. administration of concanavalin A (Con A) in BALB/c mice brought about a striking alanine aminotransferase increase, resulting in piecemeal necrosis with bridging fibrosis in the parenchyma. Using this fibrosis model, we demonstrated the kinetics of cytokine mRNA expression in liver. Transforming growth factor (TGF)-beta1, TGF-alpha, basic fibroblast growth factor (bFGF) and hepatocyte growth factor mRNAs were up-regulated after each Con A administration. Furthermore, either anti-IFN-gamma, anti-tumor necrosis factor (TNF)-alpha or anti-TGF-beta mAb given together with Con A markedly inhibited the development of hepatic fibrosis. Treatment with either anti-IFN-gamma or anti-TNF-alpha mAb also completely prevented hepatic injury; in contrast, treatment with anti-TGF-beta mAb did not. The treatment with anti-TGF-beta mAb did not affect the levels of hepatic mRNAs for either IFN-gamma or TNF-alpha after Con A injection. Treatment with either anti-IFN-gamma or anti-TNF-alpha did not affect the expression levels of TGF-beta in the liver. In conclusion, the continuous presence of both severe liver damage and up-regulation of TGF-beta synthesis is necessary to induce hepatic fibrosis in this model.
journal_name
Int Immunoljournal_title
International immunologyauthors
Kimura K,Ando K,Ohnishi H,Ishikawa T,Kakumu S,Takemura M,Muto Y,Moriwaki Hdoi
10.1093/intimm/11.9.1491subject
Has Abstractpub_date
1999-09-01 00:00:00pages
1491-500issue
9eissn
0953-8178issn
1460-2377journal_volume
11pub_type
杂志文章abstract::A recipient who received a renal graft from a living related donor showed good renal function for as long as 15 years after the withdrawal of azathioprine. The patient's creatinine clearance was maintained at 60 ml/min in spite of the administration of only 10 mg of predonisolon per day. Anti-idiotypic antibodies in t...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/1.5.503
更新日期:1989-01-01 00:00:00
abstract::The regulation of MHC class II expression by the class II transactivator (CIITA) is complex and differs in various cell types depending on the relative activity of three CIITA promoters. Here we show that, in plasma cell tumors, the deacetylase inhibitor trichostatin A (TSA) elicits PIII-CIITA but does not activate th...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxh326
更新日期:2005-11-01 00:00:00
abstract::Lymphocyte homing to lymph nodes is regulated by transient but specific interactions between lymphocytes and high endothelial venules (HEVs), the initial phase of which is mainly governed by the leukocyte adhesion molecule L-selectin, which recognizes sulfated and sialylated O-linked oligosaccharides displayed on sial...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxh128
更新日期:2004-09-01 00:00:00
abstract::CD4 T cells are not thought to play a significant role in generating an effective primary CD8 T cell response to most viral infections. We have challenged this view by demonstrating that antigen-specific CD4 T cells can indeed suppress the proliferation of antigen-specific naive CD8 T cells in response to low doses of...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxl061
更新日期:2006-08-01 00:00:00
abstract::It has proven difficult to evaluate the functional potential of germinal center (GC) B cells, including those from Peyer's patches (PP), by either in vivo or in vitro methods. Thus, rather than assess secreted Ig product as an indicator of functional potential we have instead sought to detect mRNAs related to the vari...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/3.12.1253
更新日期:1991-12-01 00:00:00
abstract::NKT follicular helper cells (NKTfh cells) are a recently discovered functional subset of CD1d-restricted NKT cells. Given the potential for NKTfh cells to promote specific antibody responses and germinal center reactions, there is much interest in determining the conditions under which NKTfh cells proliferate and/or d...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxv007
更新日期:2015-05-01 00:00:00
abstract::Southern blot analysis of genomic DNA of normal mouse thymocytes with a JH4 probe, a probe for JH4 of Igh genes, consistently showed a second band in addition to a germline band. The same band was also observed in analysis with a 5' DQ probe, a 5'-flanking sequence of DQ52, thus suggesting the use of DQ52. By analyzin...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/1.6.643
更新日期:1989-01-01 00:00:00
abstract::It has been demonstrated that in vivo T cell priming requires CD154-CD40 interaction, which is suggested to be critical in the induction of co-stimulatory activities on antigen-presenting cells (APC). In the current study, we demonstrate that in vivo administration of a high dose of a superantigen, staphylococcal ente...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxg080
更新日期:2003-07-01 00:00:00
abstract::Immune tolerance in the lung is important for preventing hypersensitivity, such as allergic asthma. Maintenance of tolerance in the lung is established by coordinated activities of poorly understood cellular and molecular mechanisms, including participation of dendritic cells (DCs). We have previously identified DC ex...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxx011
更新日期:2017-02-01 00:00:00
abstract::Programmed cell death-1 (PD-1, Pdcd1), an immunoreceptor belonging to the CD28/CTLA-4 family negatively regulates antigen receptor signaling by recruiting protein tyrosine phosphatase, SHP-2 upon interacting with either of two ligands, PD-L1 or PD-L2. Because of the wide range of ligand distribution in the body, its b...
journal_title:International immunology
pub_type: 杂志文章,评审
doi:10.1093/intimm/dxm057
更新日期:2007-07-01 00:00:00
abstract::Although there has been extensive analysis on the capacity of MHC-peptide tetramers to bind antigen-specific TCR, there have been comparatively few studies regarding the role of the CD4 and CD8 co-receptors in binding and activation by these multimeric molecules. Here, we start from the observation that different anti...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/14.1.39
更新日期:2002-01-01 00:00:00
abstract::CD25(+)CD4(+) regulatory T cells inhibit the activation of autoreactive T cells in vitro and in vivo, and suppress organ-specific autoimmune diseases. The mechanism of CD25(+)CD4(+) T cells in the regulation of experimental autoimmune encephalomyelitis (EAE) is poorly understood. To assess the role of CD25(+)CD4(+) T ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxh029
更新日期:2004-02-01 00:00:00
abstract::In this study we investigated the role of the invariant chain (li) in the presentation of hen egg lysozyme (HEL) and measles virus hemagglutinin (HA) antigens to MHC class II-restricted T hybridoma cells. Fibroblastic cells transfected with Ed or Ak genes, and supertransfected or not with the li gene, were used as ant...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/3.5.435
更新日期:1991-05-01 00:00:00
abstract::The dynamic behaviour of isolated populations of peritoneal LPS-reactive (LPSr) B lymphocytes was studied upon transfer of peritoneal cells (PerC) from C57BL/6 LPS responder into C57BL/10ScCr LPS non-responder mice. We have followed the persistence and life-span of the transferred LPSr donor B cells in the spleen and ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/2.1.73
更新日期:1990-01-01 00:00:00
abstract::Naive CD4(+) T cells rapidly proliferate to generate effector cells after encountering an antigen and small numbers survive as memory T cells in preparation for future immunological events. In the present work, adoptive transfer of naive CD4(+) T cells into RAG2(-/-) mice caused the generation of memory-type effector ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxm114
更新日期:2007-12-01 00:00:00
abstract::It has previously been described that V gamma 3 cells can proliferate extensively in vitro in the presence of different cytokines. Here, the role of cytokines in the maintenance of V gamma 3 cells in the thymus has been determined. Culture of fetal thymocytes in cell suspension for 24 h showed that, whereas immature T...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/7.5.843
更新日期:1995-05-01 00:00:00
abstract::A central tenet of vaccine development is to identify immune correlates of protection. Both plasmid-encoded gD as well as recombinant protein gD can protect mice from lethal herpes simplex virus (HSV) challenge. It is known that different vaccine modalities should induce different immune phenotypes. Yet, paradoxically...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/11.11.1763
更新日期:1999-11-01 00:00:00
abstract::IgE plus antigen-stimulated mast cells degranulate, synthesize leukotrienes and secrete cytokines. According to the coalescence model this process is initiated in specific membrane compartments termed rafts. There, enhanced levels of glycosphingolipids and cholesterol stabilize the interaction of FcepsilonRI and Lyn, ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxg120
更新日期:2003-10-01 00:00:00
abstract::CD100/Sema4D belongs to the semaphorin family, factors known to act as repulsive cues for axons during neuronal development. Mouse CD100 plays a crucial role in both humoral and cellular immunity through ligation of the lymphocyte receptor, CD72. It remains controversial, however, whether human CD100 can function thro...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxg098
更新日期:2003-08-01 00:00:00
abstract::Our aim was to investigate the quantitative relationship between inoculation doses and physiological responses to infection by Salmonella enterica serovar Enteritidis. Rats were orally inoculated with 10-10(9) c.f.u. of S. Enteritidis and monitored for 6 days. Neutrophil and delayed-type hypersensitivity (DTH) respons...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/14.2.111
更新日期:2002-02-01 00:00:00
abstract::The origin of anti-DNA antibodies remains speculative. We argue that some of these antibodies may arise inadvertently in nature during the course of a normal immune response due to their induction by antibodies which bear structures (mimotopes) that mimic DNA. These antibodies are not necessarily DNA specific but, lik...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/13.9.1099
更新日期:2001-09-01 00:00:00
abstract::Incomplete T cell antigen receptor-mediated signaling induces an unresponsive state known as anergy. Previously, we had shown that anergy can be induced in antigen-primed but not naive T cells. In this report, we found that in vitro primed T cells from IL-2R alpha-deficient mice were resistant to anergy induction in c...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxh397
更新日期:2006-05-01 00:00:00
abstract::Earlier studies have suggested that in adults the n-positive allele of the human IgG2 gene is more productive than the n-negative allele. This superiority was seen to be manifested in IgG2 antibody responses to polysaccharides, in the higher serum concentration of total IgG2 in the n/n than in -/- individuals, and in ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/2.4.317
更新日期:1990-01-01 00:00:00
abstract::Chemokine receptors (CCRs) are important co-stimulatory molecules found on many blood cells and associated with various diseases. The expression and function of CCRs on mast cells has been quite controversial. In this study, we report for the first time that murine bone marrow-derived mast cells (BMMC) express messeng...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxp066
更新日期:2009-08-01 00:00:00
abstract::The extracellular signal-regulated kinase (ERK) signaling pathway is strongly activated in response to TCR stimulation in normal T cells. However, the extent to which activation of the ERK pathway is necessary for TCR-stimulated cytokine production is not clear. We have addressed this question by use of two separate m...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/10.2.223
更新日期:1998-02-01 00:00:00
abstract::The peptide motifs of two HLA molecules, B8 and DR3(17), which are associated with autoimmune diseases including myasthenia gravis, were determined from natural peptide pools using Edman degradation. The majority of HLA-B8 ligands are nonamers preferentially terminated by leucine. As a characteristic feature of the HL...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/5.10.1229
更新日期:1993-10-01 00:00:00
abstract::Intravenous sensitization of C57BL/6 (B6) mice with class II H-2-disparate B6-C-H-2bm12(bm12) resting B cells induced anti-bm12 CD4+ T cell tolerance as shown by hyporesponsiveness in the anti-bm12 mixed lymphocyte reaction (MLR). The present study investigated the mechanism(s) of the failure of bm12 B cells to stimul...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/8.2.159
更新日期:1996-02-01 00:00:00
abstract::Tyrosine kinase-2 (Tyk2) participates in the signaling pathways of multiple cytokines in innate and acquired immunity. In the present study, we investigated the in vivo involvement of Tyk2 in anti-type II collagen antibody-induced arthritis (CAIA) using Tyk2-deficient mice. Hind paws of wild-type mice showed massive s...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxr057
更新日期:2011-09-01 00:00:00
abstract::The adaptive immune response is involved in the development and progression of atherosclerosis and IL-17A(+) cells play a role in this disease. Although elevated number of CD4(+) IL-17A(+) (Th17) and IL-17A(+)TCRγδ(+) T cells are found within murine atherosclerotic aortas and human plaques, the mechanisms governing IL...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxv068
更新日期:2016-05-01 00:00:00
abstract::Peptide-MHC class II complexes (pMHC II) are degraded by MARCH-I-mediated ubiquitination, and the stabilization of pMHC II by loss of its ubiquitination is one phenotype defining the activation of conventional dendritic cells (cDCs). However, the role of such stabilization of pMHC II in the context of T-cell activatio...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxt066
更新日期:2014-05-01 00:00:00