Abstract:
:The phosphodiesterase inhibitor oxpentifylline (OXP) has a number of potentially important immunomodulatory actions which include a selective inhibition of the Th1 subset of CD4+ cells in vitro and inhibition of tumor necrosis factor (TNF)-alpha mRNA transcription. In vivo, it has a dramatic protective effect against experimental allergic encephalomyelitis. In this animal model, tissue injury is associated with both a Th1 response and with TNF-alpha production, either of which could be targets for the protective action of OXP. In an attempt to clarify the relative importance of the Th cell subsets and TNF-alpha in pathogenesis, we investigated the effect of OXP on a Th2 model of T cell-dependent disease, mercuric chloride (HgCl2)-induced autoimmunity in the Brown Norway rat. The effects of OXP on the Th1:Th2 response, TNF-alpha mRNA transcription in spleen and ankle joints, and on the incidence and severity of arthritis and cecal vasculitis have been examined and the effects in vivo have been compared with those of a soluble TNF receptor-IgG1 fusion protein (sTNFR) that neutralizes rat TNF-alpha. In two separate experiments, OXP significantly enhanced unstimulated levels of splenic interleukin-4 (IL-4) mRNA (median 62%, of an artificial IL-4 mRNA construct, vs. 36.5% in controls) and in one experiment, exaggerated the total IgE response to HgCl2. OXP inhibited HgCl2-induced TNF-alpha mRNA transcription in spleen and ankle joints. In three separate experiments, OXP had a significant protective effect against arthritis, with the mean incidence reduced from 100% to 30% and mean peak score reduced from 7.2 to 2.59 (experiments 1 and 2). The protection against arthritis was indistinguishable from that produced by sTNFR. There was no such protection against cecal vasculitis with either OXP or sTNFR. These results demonstrate that OXP induces a shift towards a Th2 response, inhibits TNF-alpha mRNA transcription locally in joint and systemically in spleen, and has a protective effect against arthritis similar to that produced by sTNFR in the HgCl2-treated BN rat. We conclude that TNF-alpha is a critical cytokine in the pathogenesis of arthritis but not cecal vasculitis in this model, and that inhibition of TNF-alpha transcription is the most important mode of action of OXP in this situation. OXP may be a potential therapeutic agent in the treatment of other arthritides, such as human rheumatoid arthritis, in which TNF-alpha has been implicated in pathogenesis.
journal_name
Eur J Immunoljournal_title
European journal of immunologyauthors
Kiely PD,Gillespie KM,Oliveira DBdoi
10.1002/eji.1830251029subject
Has Abstractpub_date
1995-10-01 00:00:00pages
2899-906issue
10eissn
0014-2980issn
1521-4141journal_volume
25pub_type
杂志文章abstract::Adult, male Lewis rats received a single injection of 5-bromo-2'-deoxyuridine (BrdUrd) i.v. to label proliferating cells in the S phase of the cell cycle. After 1 and 24 h the thymus, bone marrow, blood, spleen, peripheral, cervical and mesenteric lymph nodes as well as Peyer's patches were removed. In cell suspension...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830190619
更新日期:1989-06-01 00:00:00
abstract::The third component of complement C3 has been implied in the stimulation of B lymphocytes to proliferation and maturation for Ig secretion. We have reinvestigated the extent of this activation with either activated or resting murine splenic lymphocytes in serum-substituted cultures. Human C3 was used in either soluble...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830150214
更新日期:1985-02-01 00:00:00
abstract::Human herpesvirus 6B (HHV-6B) is a ubiquitous pathogen with frequent reactivation observed in immunocompromised patients such as BM transplant (BMT) recipients. Adoptive immunotherapy is a promising therapeutic avenue for the treatment of opportunistic infections, including herpesviruses. While T-cell immunotherapy ca...
journal_title:European journal of immunology
pub_type: 临床试验,杂志文章
doi:10.1002/eji.201444931
更新日期:2014-12-01 00:00:00
abstract::A specialized subpopulation of T lymphocytes is reactive to the MHC class I-like molecule CD1d. It is not clear which cells are the major antigen-presenting cells in vivo in the activation of CD1-restricted immune responses. We have characterized a subset of B lymphocytes expressing six- to eightfold higher levels of ...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/(SICI)1521-4141(199910)29:10<3285::AID-IMM
更新日期:1999-10-01 00:00:00
abstract::Mercury-induced autoimmune glomerulonephritis in the Brown-Norway (BN) rat is characterized by the successive appearance of linear and granular glomerular IgG deposits. Anti-laminin autoantibodies represent the major part of the anti-glomerular basement membrane (GBM) antibodies produced in this model. Fusions were pe...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830200114
更新日期:1990-01-01 00:00:00
abstract::Programmed cell death (PCD) is involved in the physiological regulation of lymphocyte turnover, as well in the antigen-driven selection of T and B cells. Here it is shown that the immunomodulator linomide (quinoline-3-carboxamide) inhibits the apoptotic decay of peripheral T lymphocytes in response to three different ...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830240108
更新日期:1994-01-01 00:00:00
abstract::A monoclonal antibody (mAb) directed to a human leukocyte 55-kDa cell surface molecule with identical cellular distribution and biochemical properties to the CD4 was able to inhibit T cell proliferation induced either in a mixed lymphocyte culture or by activation with mAb anti-CD3, anti-CD2 or phytohemagglutinin. The...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830170205
更新日期:1987-02-01 00:00:00
abstract::Mitogens such as pokeweed mitogen, Staphylococcus aureus Cowan I, concanavalin A and phytohemagglutinin and monoclonal anti-CD antibodies were examined for their capacity to induce IgE synthesis by peripheral blood leukocytes obtained from both atopic and nonatopic individuals. While lectins failed to induce IgE synth...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830180322
更新日期:1988-03-01 00:00:00
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.201040682
更新日期:2011-04-01 00:00:00
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830230625
更新日期:1993-06-01 00:00:00
abstract::CD25+ FOXP3+CD4+ T cells (Treg) have been considered to play an important role in immune tolerance against several tumor antigens. It has also been indicated that high-level expression of FOXP3 (FOXP3high) is sufficient to confer suppressive activity to normal non-Treg. Here, we showed for the first time that vascular...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.200939887
更新日期:2010-01-01 00:00:00
abstract::Membrane-bound immunoglobulins of the IgM and IgD class are expressed on the B cell surface in association with a disulfide-linked heterodimer consisting of alpha and beta subunits. While the alpha component of the IgM antigen receptor (IgM-alpha, 34 kDa) is encoded by the B cell-specific gene mb-1, the gene coding fo...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830211012
更新日期:1991-10-01 00:00:00
abstract::Previous studies have shown that IL-10 inhibits the accessory cell functions required for production of IFN-gamma by T cells and NK cells. Our results show that although IL-10 did not induce the production of IFN-gamma by NK cells, it did enhance the ability of IL-18 to stimulate NK cell production of IFN-gamma. In ad...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/(SICI)1521-4141(199909)29:09<2658::AID-IMM
更新日期:1999-09-01 00:00:00
abstract::C57BL/10ScCr (Cr) mice carry a deletion of the Toll-like receptor 4 (tlr4) gene (i.e. they are tlr4(0/0)) and are thus refractory to LPS effects. Insertion of wild-type tlr4 transgene into the tlr4(0/0) Cr germ line endowed LPS susceptibility in the two transgenic lines created, indicating that TLR4 is the only limiti...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.200323431
更新日期:2003-03-01 00:00:00
abstract::CD82, a member of tetraspan family (tetraspanin), is a multifunctional molecule that is involved in cell activation, costimulation, and cell spreading of T cells. Here we show that immobilized anti-CD82 monoclonal antibody (mAb) as well as anti-alpha4beta1 integrin mAb induced tyrosine phosphorylation of pp105/Crk-ass...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/1521-4141(200205)32:5<1328::AID-IMMU1328>3
更新日期:2002-05-01 00:00:00
abstract::Nude mice given antigen before being given congenic T cells are specifically tolerant to that antigen and recovery of the ability to respond takes at least 2 weeks. If, after giving antigen, spleen cells are transferred to irradiated congenic recipients together with normal congenic thymocytes, the recipients usually ...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830050906
更新日期:1975-09-01 00:00:00
abstract::There is limited insight into the mechanisms involved in the counterregulation of TLR. Given the important role of TLR3/TIR domain-containing adaptor-inducing IFN-β (TRIF)-dependent signalling in innate immunity, novel insights into its modulation is of significance in the context of many physiological and pathologica...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.201040547
更新日期:2010-11-01 00:00:00
abstract::Cells from the monoclonal B cell lymphoma I.29 expressing surface IgM (mu +) are capable of differentiating in vitro to IgM secretion and of switching to IgA or IgE production in response to lipopolysaccharide (LPS) stimulation. To determine whether a single mu + B cell is capable of undertaking both differentiative p...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830170419
更新日期:1987-04-01 00:00:00
abstract::CD27, which belongs to the tumor necrosis factor receptor family, is expressed on germinal center (GC) but not on naive B cells, suggesting an important function of this molecule in the regulation of the GC reaction. We described here the expression of CD70, which is the ligand for CD27. We observed that in most tonsi...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830260508
更新日期:1996-05-01 00:00:00
abstract::Murine Thy-1+, TcR V gamma 3/V delta 1+ dendritic epidermal T cells (DETC) differ from most other T cell subsets by the absence of CD4 and CD8 antigens as well as the lack of CD5 expression. To see whether negativity for those antigens is an intrinsic feature of a given T cell population or if such triple-negative T c...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830240612
更新日期:1994-06-01 00:00:00
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journal_title:European journal of immunology
pub_type: 杂志文章
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更新日期:2014-10-01 00:00:00
abstract::We investigated whether percutaneous sensitization with different allergens through barrier-disrupted skin regulates the balance of Th1/Th2 cytokine expression. When mice were sensitized with the typical hapten picryl chloride (PiCl) by a single topical application to intact skin, there was an up-regulation in the lym...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/(SICI)1521-4141(199803)28:03<769::AID-IMMU
更新日期:1998-03-01 00:00:00
abstract::The generation of effective type 1 T helper (Th1)-cell responses is required for immunity against intracellular bacteria. However, some intracellular bacteria require interleukin (IL)-17 to drive Th1-cell immunity and subsequent protective host immunity. Here, in a model of Mycobacterium bovis Bacille Calmette-Guerin ...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.201141569
更新日期:2012-02-01 00:00:00
abstract::MHC-peptide-specific Fab antibodies binding to HLA-A*0201 complexes presenting the wild-type EAAGIGILTV (EAA) or analogue Melan-A 10-mer ELAGIGILTV (ELA) peptide were generated to study efficacy of peptide processing and presentation. None of the selected Fab antibodies detected the naturally processed EAA/HLA-A*0201 ...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.200636545
更新日期:2007-07-01 00:00:00
abstract::It is widely accepted that females have superior immune responses than males, but the ways by which sex hormones may enhance T cell responses are still poorly understood. In the present study, we analyzed the effect of estrogens on CD4 T cell activation and differentiation after immunization with exogenous antigens. W...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/immu.200310027
更新日期:2003-02-01 00:00:00
abstract::Although in vivo evidence supports a role for the murine intestinal epithelium in the extrathymic generation of certain intraepithelial T lymphocytes (IEL), no intraepithelial cells with in vitro lymphoid progenitor potential have yet been demonstrated. Using reaggregate fetal thymic organ culture techniques, we show ...
journal_title:European journal of immunology
pub_type: 杂志文章
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更新日期:2001-11-01 00:00:00
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journal_title:European journal of immunology
pub_type: 杂志文章
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更新日期:2007-09-01 00:00:00
abstract::Class I molecules, encoded by diverse alleles at several loci of the major histocompatibility complex (MHC) are assembled in the endoplasmic reticulum (ER) from heavy chain, beta2 microglobulin and peptide in association with accessory proteins of the peptide loading complex. We show here, that mutations in the alpha2...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/(SICI)1521-4141(200004)30:4<1203::AID-IMMU
更新日期:2000-04-01 00:00:00
abstract::The nonobese diabetic (NOD) mouse is a relevant model for studying human insulin-dependent diabetes mellitus (IDDM). The selective destruction of insulin-secreting cells in this model is subsequent to an autoimmune reaction directed towards the beta cells inside the islets of Langerhans of the pancreas. Given the key ...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830210511
更新日期:1991-05-01 00:00:00
abstract::Tissue factor (TF) is a transmembrane glycoprotein that plays an essential role in hemostasis by activating coagulation. TF is also expressed by monocytes/macrophages as part of the innate immune response to infections. In the current study, we determined the role of TF expressed by myeloid cells during Mycobacterium ...
journal_title:European journal of immunology
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更新日期:2016-02-01 00:00:00