Abstract:
:Peripheral T cells can be polarized towards type 1 or type 2 cytokine immune responses during TCR engagement. Because T cell selection by peptide plus self-MHC in the thymus requires TCR engagement, we hypothesized that type 1 cytokines may polarize developing T cells. We cultured thymi from BBDR rats in adult thymus organ cultures (ATOC) under type 1 cytokine conditions in the absence of exogenous antigen. Type 1 cytokine-conditioned ATOC generated cells that spontaneously secreted high levels of IFNgamma, but not IL-4. A second exposure to type 1 cytokines further increased IFNgamma secretion by these cells, most of which were blasts that expressed the activation markers CD25, CD71, CD86, and CD134. Studies using blocking antibodies and pharmacological inhibitors suggested that both IL-18 and cognate TCR-MHC/ligand interactions were important for activation. Blocking anti-MHC class I plus anti-MHC class II antibodies, neutralizing anti-IL-18 antibody, and the p38 MAP-kinase inhibitor SB203580 each reduced IFNgamma production by approximately 75-80%. Cyclosporin A, which prevents TCR signaling, inhibited IFNgamma production by approximately 50%. These data demonstrate that exposure to type 1 cytokines during intrathymic development can polarize differentiating T cells, and suggest a mechanism by which intrathymic exposure to type 1 cytokines may modulate T cell development.
journal_name
J Autoimmunjournal_title
Journal of autoimmunityauthors
Whalen BJ,Marounek J,Mordes JP,Rossini AA,Greiner DLdoi
10.1016/s0896-8411(02)00091-4subject
Has Abstractpub_date
2003-02-01 00:00:00pages
27-42issue
1eissn
0896-8411issn
1095-9157pii
S0896841102000914journal_volume
20pub_type
杂志文章abstract::Sera from autoimmune patients and normal volunteers were tested for antibodies to the A1 core protein of heteronuclear ribonucleoprotein (hnRNP) particles by ELISA and Western blot assays. The A1 protein used in these studies was produced by recombinant DNA technology. Thirty-seven per cent of patients with systemic l...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/0896-8411(88)90078-9
更新日期:1988-02-01 00:00:00
abstract::The obstetric management of women with antiphospholipid (aPL) syndrome remains controversial. Despite recent advances, the controversies have been fueled by our limited understanding of the multi-factorial causes of aPL-associated pregnancy loss and the lack of data from randomized studies. We have escaped from the na...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1006/jaut.2000.0417
更新日期:2000-09-01 00:00:00
abstract::Sjögren's syndrome (SS) is an autoimmune rheumatic disease that targets salivary and lachrymal glands, characterized by a high concentration of serum autoantibodies directed against nuclear and cytoplasmic antigens. It is known that autoantibodies can enter viable cells and this phenomenon has functional consequences ...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2006.05.001
更新日期:2006-08-01 00:00:00
abstract::Dendritic cells (DCs) are professional antigen-presenting cells (APC) with significant phenotypic heterogeneity and functional plasticity. DCs play crucial roles in initiating effective adaptive immune responses for elimination of invading pathogens and also in inducing immune tolerance toward harmless components to m...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/j.jaut.2015.07.011
更新日期:2015-09-01 00:00:00
abstract::The relationships between immunological dysfunction, loss of tolerance and hematologic malignancies have been a focus of attention in attempts to understand the appearance of a higher degree of autoimmune disease and lymphoma in children with congenital immunodeficiency. Although multiple hypotheses have been offered,...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/j.jaut.2012.09.002
更新日期:2012-12-01 00:00:00
abstract::Glutamic acid decarboxylase 65 (GAD65) is a putative autoantigen associated with the pathogenesis of type 1 diabetes (T1D). The prevalence of autoreactive CD4+ T cells towards the immunodominant GAD65(555-567) epitope in DR4 healthy and T1D subjects was investigated with class II tetramers. A slightly higher percentag...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2005.08.007
更新日期:2005-12-01 00:00:00
abstract::Ultraviolet (UV) light is a known trigger of skin and possibly systemic inflammation in systemic lupus erythematosus (SLE) patients. Although type I interferons (IFN) are upregulated in SLE skin after UV exposure, the mechanisms to explain increased UVB-induced inflammation remain unclear. This paper compares the role...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2019.06.002
更新日期:2019-09-01 00:00:00
abstract::Systemic Lupus Erythematosus (SLE) is a multisystem disease characterized by an increase in the secretion of autoantibodies. The mechanisms of autoantibody-induced disease have not been clarified. 1,25-Dihydroxy-vitamin D3 (1,25-D3) is known to be important in the regulation of normal human lymphocyte functions. Among...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/0896-8411(89)90012-7
更新日期:1989-12-01 00:00:00
abstract::Women with antiphospholipid antibodies (aPL) are at high risk for pregnancy complications, such as preeclampsia. We previously demonstrated that aPL recognizing β2GPI promote an extravillous trophoblast pro-inflammatory, anti-migratory and anti-angiogenic profile similar to that seen in preeclampsia. Since preeclampsi...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2018.12.003
更新日期:2019-03-01 00:00:00
abstract::Clinical course and changes in serum levels of antibodies to the acetylcholine receptor (a-AChR) were followed in 82 patients with myasthenia gravis during a period of 1-8 years after thymectomy. Decrease in a-AChR immediately after thymectomy was influenced by changes in a total IgG. Immunosuppressive medication affe...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/0896-8411(91)90018-8
更新日期:1991-04-01 00:00:00
abstract::Since its description in 1965, Sneddon syndrome (SNS) is usually characterized by the association of an ischemic cerebrovascular disease and a widespread livedo reticularis. The presence of many other manifestations suggests that it is a systemic syndrome. The prevalence of anti-phospholipid antibodies (aPL) is highly...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1006/jaut.2000.0418
更新日期:2000-09-01 00:00:00
abstract::The murine model of human insulin dependent diabetes mellitus (IDDM), the non-obese diabetic (NOD) mouse, develops a T cell-dependent destruction of pancreatic islets. While the target antigens are unknown, there is clearly a lack of tolerance to them. Neonatal intrathymic (i.t.) antigen injection has been successfull...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1994.1040
更新日期:1994-10-01 00:00:00
abstract:OBJECTIVE:To describe the clinical and laboratory features, as well as the precipitating factors, treatment and outcome of patients with catastrophic antiphospholipid syndrome (APS). METHODS:We analyzed the 280 patients included until September 2008 in the website based international registry of patients with catastro...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2009.02.008
更新日期:2009-05-01 00:00:00
abstract::Allogeneic hematopoietic cell transplantation (HCT) is an increasingly widely used treatment modality in hematological malignancies. Alloreactivity mediated by donor T cells (and, in some settings, by donor natural killer cells) can produce durable immunologic control or eradication of residual malignancy after alloge...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/j.jaut.2007.12.002
更新日期:2008-05-01 00:00:00
abstract::Isolated congenital heart block may be associated with autoimmune disorder such as Sjögren Syndrome and systemic lupus erythematosus. In this work we demonstrate circulating autoantibodies against neonatal heart M1 muscarinic acetylcholine receptor (mAChR) in the sera of children with congenital heart block. This anti...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.2000.0461
更新日期:2001-03-01 00:00:00
abstract::Previous studies have indicated that blood mononuclear cells from 15-20% of patients with systemic lupus erythematosus (SLE) carry elevated levels of hsp90, a heat shock protein associated with steroid receptors in cells. We analysed surface expression of hsp90 on mononuclear cells (lymphocytes and monocytes) from pat...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/0896-8411(92)90194-u
更新日期:1992-12-01 00:00:00
abstract::Previous studies have demonstrated increased expression of a laminin-like protein in labial salivary glands from Sjögren's syndrome (SS) patients. The objective of the present study was to verify the identity of this protein and to compare lymphocytic infiltration and laminin expression in minor salivary gland ductal ...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1996.0109
更新日期:1997-02-01 00:00:00
abstract:OBJECTIVES:Sicca symptoms occur in around 30% of rheumatoid arthritis (RA) patients. Herein, we examined the characteristics of RA patients bearing sicca symptomatology (RA-sicca) with a special focus on the immunohistopathological features of their labial minor salivary gland (LMSG) biopsies. METHODS:Our cohort inclu...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2016.06.008
更新日期:2016-09-01 00:00:00
abstract:OBJECTIVE:To compare the efficacy and safety of Disease-modifying antirheumatic drugs (DMARDs) and anti-TNF-α agents in patients with non-infectious non-anterior uveitis. METHODS:Single center retrospective study including adult patients with non-infectious intermediate, posterior or pan-uveitis. Outcomes were compare...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2020.102481
更新日期:2020-09-01 00:00:00
abstract:BACKGROUND:The aberrant recognition of self-nucleic acids by the innate immune system contributes to the pathology of several autoimmune diseases. Although microbial DNA and, in certain instances, self-DNA that is released from damaged cells are primarily recognized by Toll-like receptor 9 (TLR9), recent evidence sugge...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2019.06.005
更新日期:2019-12-01 00:00:00
abstract::Costimulatory molecules are cell-surface glycoproteins that can direct, modulate and fine tune immune responses. B7-2(CD86) costimulatory molecules are considered as major regulators of T cell responses, acting by appropriate interactions with the stimulatory CD28 or inhibitory CTLA-4 receptors found on T cells. Altho...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2010.06.006
更新日期:2010-11-01 00:00:00
abstract::The BB rat spontaneously develops an insulin-dependent diabetes mellitus (IDDM) that closely resembles this disease in man. The pathogenesis involves autoimmune destruction of pancreatic islet beta-cells. In the present study, a single intraperitoneal injection of complete Freund's adjuvant (CFA) in diabetes-prone (DP...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/s0896-8411(05)80034-4
更新日期:1990-12-01 00:00:00
abstract::Lupus is a systemic autoimmune disease characterized by anti-nuclear antibodies in humans and genetically susceptible NZB/W mice that can cause immune complex glomerulonephritis. T cells contribute to lupus pathogenesis by secreting pro-inflammatory cytokines such as IL-17, and by interacting with B cells and secretin...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2014.01.002
更新日期:2014-05-01 00:00:00
abstract::We have investigated the pathophysiological basis of cardiac dysfunction in autoimmune myocarditis and in the resulting dilated cardiomyopathy. To this end we utilized the myosin-induced autoimmune myocarditis model in BALB/c mice. Myocarditis has been found to be associated with massive ventricular lymphocyte infiltr...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1998.0273
更新日期:1999-05-01 00:00:00
abstract::Most autoimmune diseases (AID) are linked to an imbalance between autoreactive effector T cells (Teffs) and regulatory T cells (Tregs). While blocking Teffs with immunosuppression has long been the only therapeutic option, activating/expanding Tregs may achieve the same objective without the toxicity of immunosuppress...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.jaut.2015.01.001
更新日期:2015-04-01 00:00:00
abstract::Several polymorphisms of the insulin gene and its flanking regions (INS region) are in linkage disequilibrium and confer susceptibility to insulin-dependent diabetes (IDDM). We have analysed INS AA and AB-BB genotypes at the 1,428 FokI site (3' of the insulin gene) in 217 patients with IDDM, 402 non-diabetic first deg...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1994.1053
更新日期:1994-10-01 00:00:00
abstract::Dermatomyositis (DM) is an idiopathic inflammatory myopathy (IIM) characterized by an inflammatory infiltrate primarily affecting the skeletal muscle and skin. Most common and peculiar cutaneous lesions include Gottron's papules, Gottron's sign and heliotrope rash. Different DM subsets have been identified until now e...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/j.jaut.2013.11.005
更新日期:2014-02-01 00:00:00
abstract::It has been known for many years that bacteria can induce autoimmune responses in humans resulting in serious disease. Recent work has shown that a number of bacteria that colonize human mucosal surfaces exclusively express antigens on their surfaces which are molecular mimics of glycosphingolipids found on human cell...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1006/jaut.2000.0477
更新日期:2001-05-01 00:00:00
abstract::The development of humoral autoimmunity following organ transplantation is increasingly recognised, but of uncertain significance. We examine whether autoimmunity contributes independently to allograft rejection. In a MHC class II-mismatched murine model of chronic humoral rejection, we report that effector antinuclea...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2018.11.006
更新日期:2019-03-01 00:00:00
abstract::In some circumstances cyclosporine (CyA) induces autoimmune phenomena, and a lethal form of syngeneic graft-vs-host disease (SGVHD) can be induced in rats by the administration of CyA. Although several rat strains develop this disease, in this study, we report that of six mouse strains tested, only the DBA/2 strain de...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/0896-8411(91)90030-g
更新日期:1991-04-01 00:00:00