Abstract:
:Interleukin-2 (IL-2) gene regulation was investigated in primary cultures of highly purified human peripheral blood CD28+ T cells. Two discrete mechanisms for induction of T-cell proliferation could be distinguished by examining cell cycle progression and the expression of the IL-2 gene. Stimulation of cells by CD3 MoAb induced only transiently expressed, small amounts of IL-2 mRNA that was completely suppressed by cyclosporine. Costimulation of T cells with CD3 MoAb and either CD28 MoAb or PMA, but not calcium ionophore, induced a 50-100-fold increased in IL-2 gene expression and secretion. High levels of IL-2 gene expression could also be achieved by stimulation with calcium ionophore and PMA or CD28 MoAb and PMA, but not by CD28 MoAb plus calcium ionophore. IL-2 gene expression and T-cell proliferation induced by CD3 MoAb plus PMA or calcium ionophore plus PMA were completely suppressible by cyclosporine. In contrast, IL-2 gene expression and T-cell proliferation induced by CD28 MoAb plus PMA were unaffected by cyclosporine. The CD28 signal was dependent on new protein synthesis. Nuclear run-on transcription assays showed that anti-CD28 did not affect lymphokine transcription. A major effect of CD28 stimulation on mRNA stability was shown by studies using actinomycin D; CD28 stimulation substantially increased the half-life of IL-2 and TNF-alpha mRNA. The effects of anti-CD28 stimulation were specific for growth factors, and thus differ from previously described effects of cycloheximide on mRNA stability. These studies suggest the existence of two biochemical pathways for the induction of IL-2 production, one that occurs at the transcriptional level and is mediated by intracellular calcium release and protein kinase C and is cyclosporine-sensitive, and one that acts post-transcriptionally, is mediated by CD28 stimulation, and is cyclosporine-resistant.
journal_name
J Autoimmunjournal_title
Journal of autoimmunityauthors
June CH,Jackson KM,Ledbetter JA,Leiden JM,Lindsten T,Thompson CBdoi
10.1016/0896-8411(89)90117-0subject
Has Abstractpub_date
1989-06-01 00:00:00pages
55-65eissn
0896-8411issn
1095-9157journal_volume
2 Supplpub_type
杂志文章abstract::Dendritic cells (DCs) comprise a small population of cells in the normal thyroid. These excellent antigen-presenting cells (APCs) are thought to be involved in the initiation of thyroid autoimmune reactions. However it is not known whether the APCs involved in this process are indeed DCs, or thyrocytes. Our aims were ...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.2000.0438
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abstract::To explore the mechanisms underlying liver-directed autoimmune reactions in acute Hepatitis B Virus (HBV) infection, we followed five subjects who were identified in the early incubation phase (30-70 days before the first elevation of transaminases). We assessed serially cellular (using a T-lymphocyte migration inhibi...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/0896-8411(88)90034-0
更新日期:1988-06-01 00:00:00
abstract::The related tyrosine phosphatase-like proteins (PTP) IA-2 and IA-2beta are autoantigens of type 1 diabetes. Autoantibodies are predominantly against IA-2. We utilized the close homology between IA-2 and IA-2beta PTP domains to design chimeras and mutants in order to identify humoral IA-2-specific epitopes. Fifteen ser...
journal_title:Journal of autoimmunity
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abstract::A large number of autoimmune diseases (ADs) are more prevalent in women. The more frequent the AD and the later it appears, the more women are affected. Many ideas mainly based on hormonal and genetic factors that influence the autoimmune systems of females and males differently, have been proposed to explain this pre...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
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abstract::This paper describes some of the methodological problems related to the measurement of cyclosporin. The clinical value of the measurements following organ transplantation are discussed and those areas also applying to autoimmune indications are highlighted. It is concluded that the routine use of cyclosporin monitorin...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/0896-8411(92)90032-l
更新日期:1992-04-01 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::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::Approximately 25% of mature T cells possess two distinct cytoplasmic T cell receptor (TCR) alpha-chains, due to productive gene rearrangements of both alleles. Expression of two different alpha-chains at the cell surface is a potential risk factor for development of autoimmunity. However, it has been difficult to dete...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.2001.0504
更新日期:2001-06-01 00:00:00
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journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
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更新日期:2010-11-01 00:00:00
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journal_title:Journal of autoimmunity
pub_type: 杂志文章,多中心研究
doi:10.1016/j.jaut.2020.102512
更新日期:2020-11-01 00:00:00
abstract::Interferon regulatory factor-1 (IRF-1), a transcriptional factor, regulates type I interferon and interferon-induced genes. It was reported that IRF-1 regulates important molecules required for inflammation and immune reactions. To investigate the role of IRF-1 in the development of autoimmune diabetes, we established...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.2001.0531
更新日期:2001-09-01 00:00:00
abstract::Systemic lupus erythematosus (SLE) is a worldwide chronic autoimmune disease which may affect every organ and tissue. Genetic predisposition, environmental triggers, and the hormonal milieu, interplay in disease development and activity. Clinical manifestations and the pattern of organ involvement are widely heterogen...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/j.jaut.2018.11.001
更新日期:2019-01-01 00:00:00
abstract::The specific contributions of islet cell microenvironment during the development of autoimmune type 1 diabetes remain unclear. The aims of this study were to identify early immune-driven abnormalities in islets and pancreatic lymph nodes of NOD mice by cDNA arrays. We compared gene expression profiles of purified isle...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2004.03.007
更新日期:2004-08-01 00:00:00
abstract::The Diffuse Infiltrative Lymphocytosis Syndrome (DILS) is a rare multisystemic syndrome described in HIV-infected patients. It is characterised by CD8(+) T-cell lymphocytosis associated with a CD8(+) T-cell infiltration of multiple organs. DILS is usually seen in uncontrolled or untreated HIV infection but can also ma...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/j.jaut.2015.01.010
更新日期:2015-05-01 00:00:00
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journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2015.03.005
更新日期:2015-06-01 00:00:00
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journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2004.09.005
更新日期:2004-12-01 00:00:00
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journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.2001.0575
更新日期:2002-03-01 00:00:00
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journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1997.0158
更新日期:1997-12-01 00:00:00
abstract::The incidence of the autoimmune thyroid disease Hashimoto thyroiditis (HT) has increased in recent years, and increasing evidence supports the contribution of excess iodine intake to thyroid disease. In this study, we examined the status of autophagy and apoptosis in thyroid tissues obtained from patients with HT, and...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2016.07.008
更新日期:2016-12-01 00:00:00
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journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1997.0185
更新日期:1998-04-01 00:00:00
abstract::Congenital immune deficiency states have often been valuable experimental models of nature that have significantly enhanced our understanding of the immune response. The relationship between CD4+, CD25+ and Treg cells in the induction of autoimmunity has attracted significant attention. We report herein a male child o...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2006.04.005
更新日期:2006-08-01 00:00:00
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journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1995.0057
更新日期:1995-10-01 00:00:00
abstract::Common variable immunodeficiency (CVID) is associated with low serum immunoglobulin concentrations and an increased susceptibility to infections and autoimmune diseases. The treatment of choice for CVID patients is replacement intravenous immunoglobulin (IVIg) therapy. IVIg has been beneficial in preventing or allevia...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2010.09.006
更新日期:2011-02-01 00:00:00
abstract::Primary biliary cholangitis (PBC) is a classic autoimmune disease in which humoral, cytotoxic, and innate immune responses have been implicated with the specific targeting of a mitochondrial antigen. The mainstay of treatment remains the bile acid ursodeoxycholic acid (UDCA). Corticosteroids may have some benefits, bu...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,meta分析,评审
doi:10.1016/j.jaut.2019.04.005
更新日期:2019-07-01 00:00:00
abstract::Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is characterized by necrotizing vasculitis with the presence of pathogenic ANCA. ANCA can potentially cause neutrophil activation and induce neutrophil extracellular traps (NETs), resulting in endothelial damage as well as activation of autoreacti...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2019.102390
更新日期:2020-03-01 00:00:00
abstract::It was previously shown that BALB/c mice were susceptible to experimental autoimmune encephalomyelitis induced by immunization with proteolipid protein (PLP). To determine the encephalitogenic epitopes of PLP in BALB/c mice, mice were immunized with successively smaller pools of 20-mer peptides spanning the PLP molecu...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.2002.0619
更新日期:2002-12-01 00:00:00
abstract::Autoimmune diseases (AIDs) are believed to be multifactorial diseases that commonly involve multiple organ systems. About three fourth of the patients afflicted with AIDs are women suggesting that sex differences impact the incidence of AID. However, the proportion of females to males suffering from AID varies dependi...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/j.jaut.2011.12.001
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abstract::Salivary gland (SG) acinar-cells are susceptible to endoplasmic reticulum (ER) stress related to their secretory activity and the complexity of synthesized secretory products. SGs of Sjögren's syndrome patients (SS)-patients show signs of inflammation and altered proteostasis, associated with low IRE1α/XBP-1 pathway a...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2016.07.006
更新日期:2016-12-01 00:00:00
abstract::Glutamic acid decarboxylase (GAD) has been shown to exist as two isoforms with molecular weights of 65 kD (GAD65) and 67 kD (GAD67) in the central nervous system as well as in several non-neuronal tissues, including the pancreatic islets. Recently, this enzyme has been proposed as a key beta-cell autoantigen in insuli...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1996.0004
更新日期:1996-02-01 00:00:00
abstract::HLA-DQB1 is widely considered to be the major histocompatibility complex (MHC) susceptibility gene for type 1 diabetes (T1D). However, since inheritance of the gene in T1D is recessive, the presence of the protective HLA-DQB1 0602 allele with normal nucleotide sequence in some patients raises the question of whether H...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2007.10.006
更新日期:2008-06-01 00:00:00