Abstract:
:Blocking T cell co-stimulatory signals by anti-B7-1/B7-2 mAb is an attractive approach to treat autoimmune diseases. However, anti-B7-1/B7-2 mAb treatment is known to exacerbate autoimmune diseases through mechanisms not fully understood. Tumor necrosis factor alpha (TNF-alpha) and reactive oxygen species (ROS) also play important roles in determining the clinical outcome of autoimmune diseases. In this study, we demonstrate that the anti-B7-1 and the anti-B7-2 mAbs activate macrophages for higher induction of TNF-alpha and other effector responses such as bacterial cytotoxicity and production of ROS. Nuclear factor-kappaB (NF-kappaB) was found to be increased with anti-B7-1/B7-2 mAb treatment. Inhibition of NF-kappaB activity by over-expression of phosphorylation-defective I-kappaB alpha in anti-B7-1/B7-2 mAb-treated macrophages decreased TNF-alpha production. These data indicate that anti-B7-1 and anti-B7-2 mAbs can trigger innate-effector responses in macrophages by activating NF-kappaB-signaling pathway. Our results suggest that the B7 molecules are not only essential for induction of adaptive immune responses but also play roles in activation of innate immune responses.
journal_name
Int Immunoljournal_title
International immunologyauthors
Khan N,Ghousunnissa S,Jegadeeswaran SM,Thiagarajan D,Hasnain SE,Mukhopadhyay Sdoi
10.1093/intimm/dxm012subject
Has Abstractpub_date
2007-04-01 00:00:00pages
477-86issue
4eissn
0953-8178issn
1460-2377pii
dxm012journal_volume
19pub_type
杂志文章abstract::Experimental autoimmune encephalomyelitis (EAE) is a CD4(+) T cell-mediated, inflammatory disease with similarities to multiple sclerosis in humans. Intranasal (i.n.) administration of a myelin basic protein (MBP)-derived peptide can protect susceptible mice from EAE. The mechanisms underlying this phenomenon, however...
journal_title:International immunology
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doi:10.1093/intimm/11.6.871
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journal_title:International immunology
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abstract::Mice with a targeted deletion of the T-bet gene exhibit spontaneous airway hyperresponsiveness (AHR), airway inflammation, enhanced recovery of T(h)2 cytokines from bronchoalveolar lavage fluid, sub-epithelial collagen deposition and myofibroblast transformation. Here we analyze the mechanisms responsible for the chro...
journal_title:International immunology
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更新日期:2005-08-01 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
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journal_title:International immunology
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journal_title:International immunology
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journal_title:International immunology
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doi:10.1093/intimm/6.9.1323
更新日期:1994-09-01 00:00:00
abstract::Neural stem cells (NSCs) transplantation has been proposed as a means of restoring damaged brain tissue, a possibility rendered more likely by reports of low NSCs immunogenicity in various experimental models because of low expression of MHC class I and II as well as co-stimulatory molecules. We investigated the immun...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxm079
更新日期:2007-09-01 00:00:00
abstract::Interleukin 6 (IL-6) is involved both in immune responses and in inflammation, hematopoiesis, bone metabolism and embryonic development. IL-6 plays roles in chronic inflammation (closely related to chronic inflammatory diseases, autoimmune diseases and cancer) and even in the cytokine storm of corona virus disease 201...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxaa078
更新日期:2020-12-18 00:00:00
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journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxm103
更新日期:2007-12-01 00:00:00
abstract::Tyrosine kinase 2 (Tyk2), a member of the Jak kinase family, mediates signals triggered by various cytokines, which are related to the pathogenesis of psoriasis. In this study, we investigated the role of Tyk2 in IL-23-induced psoriasis-like skin inflammation. Tyk2(-/-) mice when injected with IL-23 showed significant...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxt062
更新日期:2014-05-01 00:00:00
abstract::Human intestinal intraepithelial lymphocytes (iIEL) are a unique population of predominantly CD8 alpha beta+, TCR alpha beta+ lymphocytes and, to a lesser extent, TCP gamma delta+ lymphocytes that proliferate poorly to anti-CD3 mitogenic signals but display significant cytolytic activity. Studies in mouse model system...
journal_title:International immunology
pub_type: 杂志文章,评审
doi:10.1093/intimm/7.8.1237
更新日期:1995-08-01 00:00:00
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journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxaa070
更新日期:2020-10-10 00:00:00
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journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxaa027
更新日期:2020-10-20 00:00:00
abstract::The lectin complement pathway is initiated by binding of mannose-binding lectin (MBL) and MBL-associated serine protease (MASP) to carbohydrates. In the human lectin pathway, MASP-1 and MASP-2 are involved in the proteolysis of C4, C2 and C3. Here we report that the human MBL-MASP complex contains a new 22 kDa protein...
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pub_type: 杂志文章
doi:10.1093/intimm/11.5.859
更新日期:1999-05-01 00:00:00
abstract::A canonical pre-TCR/TCR signaling pathway critical for thymic T cell development involves sequential phosphorylation and signaling through Lck, Zap70, Lat and Slp76. However, we and others have previously reported that genomic deletion of c-Cbl (Cbl) partially or completely reverses the defects in thymic development i...
journal_title:International immunology
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更新日期:2015-05-01 00:00:00
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journal_title:International immunology
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doi:10.1093/intimm/dxm087
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journal_title:International immunology
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doi:10.1093/intimm/6.5.693
更新日期:1994-05-01 00:00:00
abstract::Antibody to phosphatidyl choline (PtC) is produced spontaneously in mice, by approximately 2-10% of naturally occurring CD5+ (B1) B cells in the peritoneum. Much of this antibody is encoded by the VH11 gene associated with a specific V kappa 9 gene. Constraints on the size and structure of the H chain CDR3 have been d...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/5.11.1365
更新日期:1993-11-01 00:00:00
abstract::Kit/CD117 plays a crucial role in the cell-cell and cell-matrix adhesion of mammalian mast cells (MCs); however, it is unclear whether other adhesion molecule(s) perform important roles in the adhesion of MCs. In the present study, we show a novel Kit-independent adhesion mechanism of mouse cultured MCs mediated by No...
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更新日期:2019-02-15 00:00:00
abstract::Immunoglobulin (IG:) genes are hypermutated in mature B cells after interaction with antigen and T cells in a germinal center reaction. We and others have recently shown that the human BCL6 gene is also hypermutated in human peripheral blood memory B cells and tonsils. A preliminary analysis of other non-Ig genes (c-M...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/12.7.1085
更新日期:2000-07-01 00:00:00
abstract::We have analyzed transcripts encoding the variable regions of Ig heavy chains from adult and fetal bovine splenocytes and bovine x mouse heterohybridomas. The 13 adult, seven fetal and two heterohybridomas transcripts as well as the six genes that were sequenced had > 83% identity to each other in the VH-encoded regio...
journal_title:International immunology
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pub_type: 杂志文章
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更新日期:2020-08-31 00:00:00
abstract::The chaperone glucose-regulated protein 94 (GRP94) has long been used to augment peptide presentation to T cells. This chaperone binds antigenic peptides, binds to receptors on professional antigen-presenting cells (APCs), activates these cells and after internalization, transfers the peptides to MHC class I for activ...
journal_title:International immunology
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更新日期:2006-07-01 00:00:00
abstract::In vivo administration of NKT cell ligand, alpha-galactosylceramide (alpha-GalCer), caused the activation of NKT cells to induce a strong NK activity and cytokine production by CD1d-restricted mechanisms. Surprisingly, we also found that alpha-GalCer induced the activation of immunoregulatory cells involved in acquire...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/12.7.987
更新日期:2000-07-01 00:00:00