Abstract:
:The production of IgE, a main player in allergic disorders such as asthma and atopic dermatitis, is strictly regulated and the serum concentrations of IgE are normally kept at a much lower level than other isotypes. We found that mice deficient for the p85alpha regulatory subunit of class IA phosphoinositide 3-kinase (PI3K) produced increasing amounts of serum IgE. Purified p85alpha-/- B cells produced more IgE than wild-type B cells in vitro in response to anti-CD40 mAb and IL-4. PI3K inhibitors wortmannin and IC87114 enhanced IgE production by wild-type B cells stimulated with anti-CD40 mAb and IL-4. Under the same condition, antigen receptor cross-linking induced the expression of inhibitor of differentiation-2 and suppressed the expression of activation-induced cytidine deaminase and class switch recombination (CSR) in a PI3K-dependent manner. IgE production was also suppressed in a concentrated cell culture condition, which was completely reversed by PI3K inhibition. The selective suppression of IgE production by PI3K was also observed at a protein level after CSR. Our results indicate that PI3K negatively regulates IgE production at both CSR and protein levels.
journal_name
Int Immunoljournal_title
International immunologyauthors
Doi T,Obayashi K,Kadowaki T,Fujii H,Koyasu Sdoi
10.1093/intimm/dxn009subject
Has Abstractpub_date
2008-04-01 00:00:00pages
499-508issue
4eissn
0953-8178issn
1460-2377pii
dxn009journal_volume
20pub_type
杂志文章abstract::Monoclonal non-specific suppressor factor (MNSF), a lymphokine produced by a murine hybridoma, was originally found to inhibit the generation of lipopolysaccharide (LPS)-induced Ig-secreting cells. Most recently, we demonstrated the recombinant form of the ubiquitin-like segment (rUbi-L) or MNSF beta, an isoform of MN...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/8.11.1659
更新日期:1996-11-01 00:00:00
abstract::We have previously shown that the surface alphabeta T cell antigen receptor (TCR).CD3 complex borne by human CD4(+) and CD8(+) T lymphocytes can be distinguished using mAbs. Using two unrelated sets of antibodies, we have now extended this finding to the surface alphabetaTCR.CD3 of seven additional mammalian species (...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxn081
更新日期:2008-10-01 00:00:00
abstract::LPS-binding protein (LBP) can facilitate the transfer of cell wall components of both Gram-negative bacteria (LPS) and Gram-positive bacteria (lipoteichoic acid) to inflammatory cells. Although LBP is predominantly produced in the liver, recent studies have indicated that this protein is also synthesized locally in th...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxh161
更新日期:2004-11-01 00:00:00
abstract::We have examined the role in B cell activation of ornithine decarboxylase (ODC), the labile rate-limiting enzyme in the synthesis of polyamines thought to be required for S phase entry in all cells. When small resting mouse splenic B cells were stimulated with the mitogenic agents phorbol myristate acetate (PMA) plus ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/6.11.1777
更新日期:1994-11-01 00:00:00
abstract::Behçet's syndrome (BS) is a systemic inflammatory disorder with unknown etiology. Features of both innate and adaptive immunity have been claimed in the pathogenesis of BS. To test the possible dysregulation of the NLRP3/cryopyrin (Nod-like receptor with a pyrin domain 3) inflammasome, as a result of mutation(s), we p...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxt046
更新日期:2014-02-01 00:00:00
abstract::Antigen engagement of the TCR may lead to activation of mature T cells while inducing deletion or positive selection of immature thymocytes. Using thymocytes from TCR transgenic mice recognizing the allo-antigen H-2Kb we investigated whether double-positive CD4+CD8+ (DP) thymocytes constitute a particular developmenta...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/8.9.1421
更新日期:1996-09-01 00:00:00
abstract::Toll-like receptor 4 (TLR4) recognizes lipopolysaccharide (LPS). MD-2 is associated with TLR4 and imparts LPS responsiveness to it. Little is known, however, as to whether MD-2 directly regulates LPS recognition by TLR4. To address the issue, we took advantage of a species-specific pharmacology of lipid IVa, an analog...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/13.12.1595
更新日期:2001-12-01 00:00:00
abstract::CD69, an 'activation marker' that is rapidly induced on mature T cells after stimulation through the T cell antigen receptor (TCR) was found to be expressed on approximately 10% of normal thymocytes. All of these CD69+ thymocytes express alpha beta TCR, and they include both TCRlowCD4+CD8+ and TCRhighCD4+CD8- or CD4-C...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/5.9.1139
更新日期:1993-09-01 00:00:00
abstract::Susceptibility and resistance to type 1 diabetes are associated with MHC class II alleles that carry non-Asp and Asp at residue 57 of their beta chain respectively. The effect of Asp or non-Aspbeta57 may relate to a differential ability of distinct class II molecules to bind specific immuno-pathogenic peptides. Recent...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/10.8.1229
更新日期:1998-08-01 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
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
pub_type: 杂志文章
doi:10.1093/intimm/dxh397
更新日期:2006-05-01 00:00:00
abstract::Structural and functional aspects of the accessory molecule lymphocyte function associated antigen (LFA)-3 (CD58) have been examined following the transfection of DAP.3 and P815 cells with a cDNA clone encoding the glycosyl phosphatidylinositol (GPI)-linked form of human LFA-3. Despite earlier observations that DAP.3 ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/4.6.673
更新日期:1992-06-01 00:00:00
abstract::The human chymase (HC) is a major granule constituent of mast cells (MCs) residing in the connective tissue and the sub-mucosa. Although many potential substrates have been described for this important MC enzyme, its full range of in vivo substrates has most likely not yet been identified. A major step toward a better...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxn128
更新日期:2009-01-01 00:00:00
abstract::The kinetics of kappa light (kappa L) chain gene rearrangement and expression on mRNA and protein level has been studied with four stromal cell/IL-7 reactive, long-term in vitro proliferating pre-B cell lines and clones, two from fetal liver of normal mice and two from fetal liver of E microH-bcl-2 transgenic (bcl-2-t...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/5.12.1609
更新日期:1993-12-01 00:00:00
abstract::A subclone (160b) of the human B cell (Karpas 160) was shown to produce a novel cytotoxic lymphokine [Factor 2 (F2)] in addition to tumour necrosis factor alpha (TNF-alpha) and beta (TNF-beta). F2 was found to have selective toxicity to numerous human tumour cell lines, particularly the erythroleukaemic cell line K562...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/4.4.519
更新日期:1992-04-01 00:00:00
abstract::Malaria infection induces the production of serum antibodies to a variety of malaria antigens but the prevalence of antibodies to any particular antigen is typically much less than 100%. It has been assumed that non-responsiveness to defined antigens in malaria immune subjects is due to HLS-mediated restriction of the...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/8.6.905
更新日期:1996-06-01 00:00:00
abstract::Absence of transforming growth factor-beta (TGF-beta) signaling to T cells in mice results in an increase in T cell numbers, an activated CD44 high, CD69-, CD25- T cell phenotype and a T cell-mediated injury to many organs. It is not known if such T cell activation in the absence of TGF-beta signaling is spontaneous o...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxh233
更新日期:2005-05-01 00:00:00
abstract::Heat shock protein (Hsp) 60 is thought to function as endogenous danger signal by activating professional antigen-presenting cells (APC) through toll-like receptor (TLR) 4 and CD14, a mechanism that is also used by bacterial LPS. We recently showed that Hsp60 binds LPS and enhances LPS-induced immune stimulation. On t...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxn003
更新日期:2008-03-01 00:00:00
abstract::HLA-G, a human MHC class I molecule expressed on the trophoblast during pregnancy, was expressed in transgenic mice by recombining the HLA-G gene with a transcriptional promoter from a murine H-2 MHC class I gene. Skin grafts from HLA-G transgenic mice were rejected by non-transgenic mice showing that HLA-G behaves as...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/9.5.645
更新日期:1997-05-01 00:00:00
abstract::Intravenous sensitization of C57BL/6 (B6) mice with class II H-2-disparate B6-C-H-2bm12(bm12) resting B cells induced anti-bm12 CD4+ T cell tolerance as shown by hyporesponsiveness in the anti-bm12 mixed lymphocyte reaction (MLR). The present study investigated the mechanism(s) of the failure of bm12 B cells to stimul...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/8.2.159
更新日期:1996-02-01 00:00:00
abstract::Dendritic cells (DC) are key players in the initiation and modulation of adaptive immune responses due to their ability to acquire and present antigen and stimulate T cells. For the induction of effector T cell functions, antigen must be presented by activated DC. In this study, we have compared uptake of antigen by m...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxp053
更新日期:2009-07-01 00:00:00
abstract::To develop a comprehensive catalogue of phenotypic and functional parameters of human CD4(+) T cell differentiation stages, we have performed microarray gene expression profiling on subpopulations of human thymocytes and circulating naive CD4(+) T cells, including CD3(-)CD4(+)CD8(-) intrathymic T progenitor cells, CD3...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxh112
更新日期:2004-08-01 00:00:00
abstract::Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired type hemolytic disorder. Hematopoietic cells of patients with PNH are deficient in glycosylphosphatidylinositol (GPI) anchored membrane proteins. Since some membrane-bound complement inhibitors, such as CD59 and decay accelerating factor (DAF), are GPI anchored ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/4.11.1263
更新日期:1992-11-01 00:00:00
abstract::Earlier studies have demonstrated an over-expression of 9-O-acetylated sialoglycoconjugates (9-OAcSGs) on lymphoblasts, concomitant with high titers of anti-9-OAcSGs in childhood acute lymphoblastic leukemia (ALL). The present study was aimed to evaluate whether this high induction of anti-9-OAcSGs at disease presenta...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxh198
更新日期:2005-02-01 00:00:00
abstract::After a 3 week course (approximately), during which there is marked lymphoid hyperplasia, Trypanosoma musculi infections in young-adult mice are cured by an immune mechanism involving antibodies of the IgG2a isotype. Both the lymphoid hyperplasia and IgG2a antibody response are T-cell-dependent events and both process...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/6.8.1107
更新日期:1994-08-01 00:00:00
abstract::Stroke is one of the major causes of lethality and disability, yet few effective therapies have been established for ischemic stroke. Inflammation in the ischemic brain is induced by the infiltration and subsequent activation of immune cells. Loss of cerebral blood flow and ischemic brain-cell death trigger the activa...
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::It has been demonstrated that in vivo T cell priming requires CD154-CD40 interaction, which is suggested to be critical in the induction of co-stimulatory activities on antigen-presenting cells (APC). In the current study, we demonstrate that in vivo administration of a high dose of a superantigen, staphylococcal ente...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxg080
更新日期:2003-07-01 00:00:00
abstract::Cytotoxic T lymphocyte (CTL) mediated killing has classically been associated with a high level of specificity for the target cell. However, when CTL clones and specific target cells were copelleted with innocent bystander cells for which the CTL was not specific, these bystander cells were also lysed. Bystander lysis...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/5.9.1049
更新日期:1993-09-01 00:00:00
abstract::Cyclosporin A (CsA) prevents most immature thymocytes from progressing to a mature phenotype and blocks the deletion of T cells that express self-specific TCR in the small population of cells that achieve maturity. The latter effect may explain the paradoxical observation that this immunosuppressive drug can induce au...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/4.12.1341
更新日期:1992-12-01 00:00:00
abstract::The co-existence of tumor specific immunity with a progressing tumor is observed in a variety of experimental systems and remains one of the major paradoxes of tumor immunology. We now report that a human melanoma cell line (SMC) expressing MHC class II was able to induce clonal anergy in a specific, MHC-restricted CD...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/5.12.1501
更新日期:1993-12-01 00:00:00