Abstract:
:T and B lymphocytes are central regulators and effectors of immune responses and are believed to have a key role in many autoimmune diseases. Targeting the activation or effector function of lymphocytes is a potentially effective approach to treat autoimmunity. Typically, T-cell activation occurs after engagement of the T-cell receptor with its cognate peptide-major histocompatibility complex (signal 1) and subsequent engagement of co-stimulatory molecules (signal 2). This "second signal" contributes to T-cell activation by promoting proliferation, survival, and effector function. In general, activation in the absence of co-stimulation leads to a reduced immune response, anergy, or even tolerance. B-cell activation similarly requires co-stimulation for the development of complete effector function. The most potent co-stimulatory molecules identified to date are CD28 for T-cells and CD40 for B-cells. Both molecules are recognized for their potential as immune modulators; however, thus far neither molecule has been successfully targeted directly for the treatment of autoimmune disease. The only current therapy to target either of these pathways is cytotoxic T-lymphocyte antigen-4 (CTLA-4-Ig), which indirectly blocks CD28 signaling and has proven efficacy in rheumatoid arthritis and juvenile idiopathic arthritis patients. In addition to CD28 and CD40, an array of other co-stimulatory as well as inhibitory pathways has recently been identified and scientists are just beginning to understand how these different signaling pathways interact to regulate lymphocyte activation. In the more than two decades since the discovery of the first co-stimulatory molecule, the full clinical potential of these pathways is yet to be realized. In this review, we will primarily focus on CD28 and CD40 which are the most clinically validated co-stimulatory pathways, and briefly summarize and discuss some of the other T-cell co-stimulatory molecules.
journal_name
Autoimmunityjournal_title
Autoimmunityauthors
Felix NJ,Suri A,Salter-Cid L,Nadler SG,Gujrathi S,Corbo M,Aranda Rdoi
10.3109/08916931003674741subject
Has Abstractpub_date
2010-11-01 00:00:00pages
514-25issue
7eissn
0891-6934issn
1607-842Xjournal_volume
43pub_type
杂志文章,评审相关文献
AUTOIMMUNITY文献大全abstract:INTRODUCTION:Autoimmune diseases, such as celiac disease (CD) and diabetes mellitus type 1, tend to co-occur within the same patient. The prevalence of CD in diabetic children is higher than in the general population, and is estimated to be 0.6-16.4%. The diagnosis of CD is based on histopathological examination and se...
journal_title:Autoimmunity
pub_type: 杂志文章
doi:10.1080/08916934.2018.1427226
更新日期:2018-03-01 00:00:00
abstract::There is a need for methods to improve the diagnosis, patient staging and evaluation of therapeutic response in patients with autoimmune conditions to improve patient care. Inflammatory bowel disease (IBD) and rheumatoid arthritis (RA) are two inflammatory diseases characterized by involvement of innate and adaptive i...
journal_title:Autoimmunity
pub_type: 杂志文章,评审
doi:10.3109/08916931003674766
更新日期:2010-11-01 00:00:00
abstract::In the 1950s, the discovery of autoantibodies produced by B cells seemed to provide a compelling mechanism underlying autoimmune diseases. The discovery of T regulatory cells and other T helper cell subsets shifted the field back towards a T cell central view. The success of rituxan, a chimeric mAb targeting CD20 on B...
journal_title:Autoimmunity
pub_type: 杂志文章,评审
doi:10.3109/08916934.2013.856006
更新日期:2014-02-01 00:00:00
abstract::A large number of malaria immune persons from Eastern India were found to possess antibodies to the ribosomal phosphoprotein P0 (PfP0) of the human malarial parasite Plasmodium falciparum. The characterization of PfP0 has been reported recently, and it has been shown that antibodies against PfP0 inhibit P. falciparum ...
journal_title:Autoimmunity
pub_type: 杂志文章
doi:10.1080/08916934.2002.11873702
更新日期:2001-01-01 00:00:00
abstract::Subcutaneous insulin treatment of young diabetes prone BB rats has been shown previously to suppress the development of autoimmune diabetes. In this study the hypothesis was tested that exogenous insulin may deviate the autoimmune process by acting on the Th1/Th2 cytokine balance in the pancreas. BB rats were implante...
journal_title:Autoimmunity
pub_type: 杂志文章
doi:10.3109/08916939709009544
更新日期:1997-01-01 00:00:00
abstract::Antineutrophil cytoplasmic antibodies (ANCA) are important serologic markers for ANCA-associated vasculitis (AAV). Our previous studies in propylthiouracil (PTU)-induced AAV demonstrated that withdrawal of PTU resulted in clinical remission and significant decrease of avidity of PTU-induced myeloperoxidase (MPO)-ANCA....
journal_title:Autoimmunity
pub_type: 杂志文章
doi:10.1080/08916930802668594
更新日期:2009-03-01 00:00:00
abstract::Pemphigus vulgaris is a potentially fatal autoimmune mucocutaneous disease associated with production of IgG autoantibodies to desmoglein 3, a 130 kDa epidermal protein. To further characterize the epitope(s) of pemphigus vulgaris antigen we established two human-human hybridoma by fusion of the peripheral blood monon...
journal_title:Autoimmunity
pub_type: 杂志文章
doi:10.1080/08916930290016655
更新日期:2002-03-01 00:00:00
abstract::Anti-phospholipid syndrome (APS) is an autoimmune disorder characterized by the presence of autoantibody (AAb) to phospholipid (PL)-binding proteins, such as beta2-glycoprotein I (beta2GPI), and clinical manifestations including thrombosis and/or recurrent pregnancy loss. beta2GPI-reactive T cells are clearly implicat...
journal_title:Autoimmunity
pub_type: 杂志文章
doi:10.1080/08916930902828254
更新日期:2009-05-01 00:00:00
abstract:BACKGROUND:T follicular helper (Tfh) cells are known to regulate humoral immune response. In this study we examined the correlation of different subsets of peripheral blood Tfh cells in patients with diabetic nephropathy (DN). METHODS:A total of 23 DN patients and 15 healthy controls (HC) were investigated for various...
journal_title:Autoimmunity
pub_type: 杂志文章
doi:10.1080/08916934.2016.1196677
更新日期:2016-09-01 00:00:00
abstract::TGPO-aAb is a bispecific antibody which binds to thyroglobulin as well as thyroid peroxidase. It is supposed to be raised in some patients with autoimmune thyroid disease. We investigated 205 patients suffering from Graves' disease (n = 81), Hashimoto's thyroiditis (n = 36), toxic nodular goitre (n = 50), differentiat...
journal_title:Autoimmunity
pub_type: 杂志文章
doi:10.3109/08916939908994744
更新日期:1999-01-01 00:00:00
abstract::Infectious agents have been implicated in the etiopathogenesis of various vasculitides via numerous and overlapping mechanisms including direct microbial invasion of endothelial cells, immune complex mediated vessel wall damage and stimulation of autoreactive B and/or T cells through molecular mimicry and superantigen...
journal_title:Autoimmunity
pub_type: 杂志文章,评审
doi:10.1080/08916930802613210
更新日期:2009-08-01 00:00:00
abstract::A flow cytometry-based phagocytosis assay was developed and utilized to measure the LE cell phenomenon at the single cell level in vitro. Since the lupus erythematosus (LE) cell phenomenon is a special form of necro-phagocytosis in the presence of anti-dsDNA antibodies, dead substrate cells or chicken erythrocytes nuc...
journal_title:Autoimmunity
pub_type: 杂志文章
doi:10.1080/08916930310001630325
更新日期:2004-02-01 00:00:00
abstract::Primary biliary cirrhosis (PBC) is characterised by immune-mediated damage to the intra-hepatic biliary epithelial cells (BEC). Immuno-modulatory/suppressive therapy represents, therefore, alogical approach to treatment in this disease. Conventional immuno-suppressive and immuno-modulatory agents suffer from the bread...
journal_title:Autoimmunity
pub_type: 杂志文章
doi:10.1080/0891693021000054084
更新日期:2002-12-01 00:00:00
abstract::Rheumatoid factors (RF), which are antibodies (Ab) with specificity directed against gamma (?) globulins, are the commonest auto-Ab ever described in man. Some of them are referred to as agglutinating RF, others designated non-agglutinating RF. Not only do these characterize rheumatoid arthritis (RA), but they are als...
journal_title:Autoimmunity
pub_type: 杂志文章,评审
doi:10.1080/08916930400022574
更新日期:2005-02-01 00:00:00
abstract::Proteinase 3 (PR3)-specific antineutrophil cytoplasmic autoantibodies (PR3-ANCA) recognize conformational epitopes on PR3. This study evaluates PR3-ANCA target epitopes utilizing a novel recombinant PR3 (rPR3) produced to accommodate manipulations of the N-terminal domain. The rPR3 molecule contains an N-terminus six ...
journal_title:Autoimmunity
pub_type: 杂志文章
doi:10.1080/08916930701680104
更新日期:2007-11-01 00:00:00
abstract::We analyzed morphologically autoimmune disease in MRL/MpJ mice bearing both the Yaa and lpr genes (MRL-lpr,Yaa mice), and compared it with that in MRL/MpJ-lpr/lpr (MRL-lpr) mice, in order to examine the effect of the Yaa gene on lpr-induced tissue-specific immunopathologies. MRL-lpr,Yaa male mice developed glomerulone...
journal_title:Autoimmunity
pub_type: 杂志文章
doi:10.3109/08916939309079229
更新日期:1993-01-01 00:00:00
abstract::The presence of autoimmune rheumatic diseases in several members of the same family, the concurrence of autoimmune rheumatic with non-rheumatic diseases in relatives of patients, the presence of autoantibodies in sera from healthy relatives of autoimmune-disease patients, the development of two or more autoimmune rheu...
journal_title:Autoimmunity
pub_type: 杂志文章
doi:10.1080/08916930500050145
更新日期:2005-05-01 00:00:00
abstract::Peripheral blood B lymphocytes of multiple sclerosis (MS) patients and control persons were transformed with Epstein-Barr virus. Antibody production of transformed cells against isolated human myelin was investigated by enzyme-linked immunosorbent assay (ELISA). Cells producing reactive antibodies were cloned and prop...
journal_title:Autoimmunity
pub_type: 杂志文章
doi:10.3109/08916938909029146
更新日期:1989-01-01 00:00:00
abstract::Recent years have witnessed an explosive growth in available biological data pertaining to autoimmunity research. This includes a tremendous quantity of sequence data (biological structures, genetic and physical maps, pathways, etc.) generated by genome and proteome projects plus extensive clinical and epidemiological...
journal_title:Autoimmunity
pub_type: 杂志文章,评审
doi:10.1080/08916930601062437
更新日期:2006-12-01 00:00:00
abstract::The allograft inflammatory factor-1 (AIF-1) is a 17 kDa interferon-gamma (IFN-gamma) inducible Ca(2+)-binding EF-hand protein that is encoded within the HLA class III genomic region. Three proteins including ionized Ca(2+)-binding adaptor 1, microglia response factor-1, and daintain are identical with AIF-1. The expre...
journal_title:Autoimmunity
pub_type: 杂志文章,评审
doi:10.1080/08916930601083946
更新日期:2007-03-01 00:00:00
abstract::CNS demyelinating inflammatory disease can be a multifactorial process mediated by cellular and antibody-mediated immune processes. Myelin basic protein (MBP)-specific T cells and pathogenic 8-18C5 antibody, specific for a myelin/oligodendrocyte glycoprotein (MOG), a minor component of CNS white matter, can coexist in...
journal_title:Autoimmunity
pub_type: 杂志文章
doi:10.3109/08916938909014690
更新日期:1989-01-01 00:00:00
abstract::Interleukin 1beta (IL-1) is cytotoxic to rat pancreatic beta-cells in vitro, and increased expression of IL-1 mRNA is found in the islets of Langerhans during development of diabetes in BB/Wor/Mol-BB2 (BB-DP) rats and NOD mice. It has been proposed that IL-1 induces a race between protective and deleterious proteins i...
journal_title:Autoimmunity
pub_type: 杂志文章
doi:10.3109/08916930008995982
更新日期:2000-01-01 00:00:00
abstract:OBJECTIVE:The objective of this study is to characterise the functionally relevant minor lymphocyte subpopulations in whole blood of multiple sclerosis (MS) patients and their potential utility as biomarkers for treatment follow up. MATERIAL AND METHODS:Peripheral blood from 40 healthy donors (HD) and 66 MS patients [...
journal_title:Autoimmunity
pub_type: 杂志文章
doi:10.3109/08916934.2016.1138271
更新日期:2016-06-01 00:00:00
abstract::Type 1 diabetes mellitus (T1DM) is the result of the autoimmune response against pancreatic insulin producing beta cells. This autoimmune response begins months or even years before the first presentation of signs and symptoms of hyperglycemia and at the time of clinical diagnosis near 30% of beta-cell mass still rema...
journal_title:Autoimmunity
pub_type: 杂志文章
doi:10.1080/08916930802200208
更新日期:2008-12-01 00:00:00
abstract::It has been shown that cationic anti-DNA antibodies have nephritogenic potential in murine models of lupus nephritis. More recently, we have reported that there is a close relationship between the presence of circulating cationic anti-DNA antibodies and the development of lupus nephritis in humans, and that the cation...
journal_title:Autoimmunity
pub_type: 杂志文章
doi:10.3109/08916939409009538
更新日期:1994-01-01 00:00:00
abstract::Glucocorticoids (GCs) strongly impact on different T cell subsets inducing generally immunosuppressive effects, whereas much less is known about the effect of GC on natural killer (NK) cells. The aims of this study were to investigate the effects of GC on T cell functions, including T cell-mediated anti-tumor immune r...
journal_title:Autoimmunity
pub_type: 杂志文章
doi:10.3109/08916934.2014.959164
更新日期:2015-03-01 00:00:00
abstract::Multiple sclerosis (MS) is a highly detrimental autoimmune disease of the central nervous system. There is no cure for it but the treatment typically focuses on subsiding severity and recurrence of the disease. Experimental autoimmune encephalomyelitis (EAE) is an animal model of MS. It is characterized by frequent re...
journal_title:Autoimmunity
pub_type: 杂志文章
doi:10.1080/08916934.2017.1332185
更新日期:2017-08-01 00:00:00
abstract::Epstein-Barr virus (EBV) is a human herpesvirus hiding in a latent form in memory B cells in the majority of the world population. Although, primary EBV infection is asymptomatic or causes a self-limiting disease, infectious mononucleosis, the virus is associated with a wide variety of neoplasms developing in immunosu...
journal_title:Autoimmunity
pub_type: 杂志文章,评审
doi:10.1080/08916930802024772
更新日期:2008-05-01 00:00:00
abstract::The G to A transition at position +1057 single nucleotide polymorphism site in CD86 gene results in the alanine to threonine substitution, which further affects the antigen-presenting cells' signal transduction. Thus, the purpose of this study was to determine the association between CD86 +1057G/A polymorphism and the...
journal_title:Autoimmunity
pub_type: 杂志文章
doi:10.3109/08916934.2014.921813
更新日期:2014-11-01 00:00:00
abstract::Allogeneic hematopoietic stem cell transplantation (HSCT) offers the unique opportunity to replace a diseased hematopoietic or immune system by healthy donor cells. Proof of principle comes from experimental animal data, from the experience with severe aplastic anemia, from observations of patients with concomitant au...
journal_title:Autoimmunity
pub_type: 杂志文章
doi:10.1080/08916930802197677
更新日期:2008-12-01 00:00:00