T-cell function is partially maintained in the absence of class IA phosphoinositide 3-kinase signaling.

Abstract:

:The class IA subgroup of phosphoinositide 3-kinase (PI3K) is activated downstream of antigen receptors, costimulatory molecules, and cytokine receptors on lymphocytes. Targeted deletion of individual genes for class IA regulatory subunits severely impairs the development and function of B cells but not T cells. Here we analyze conditional mutant mice in which thymocytes and T cells lack the major class IA regulatory subunits p85alpha, p55alpha, p50alpha, and p85beta. These cells exhibit nearly complete loss of PI3K signaling downstream of the T-cell receptor (TCR) and CD28. Nevertheless, T-cell development is largely unperturbed, and peripheral T cells show only partial impairments in proliferation and cytokine production in vitro. Both genetic and pharmacologic experiments suggest that class IA PI3K signaling plays a limited role in T-cell proliferation driven by TCR/CD28 clustering. In vivo, class IA-deficient T cells provide reduced help to B cells but show normal ability to mediate antiviral immunity. Together these findings provide definitive evidence that class IA PI3K regulatory subunits are essential for a subset of T-cell functions while challenging the notion that this signaling mechanism is a critical mediator of costimulatory signals downstream of CD28.

journal_name

Blood

journal_title

Blood

authors

Deane JA,Kharas MG,Oak JS,Stiles LN,Luo J,Moore TI,Ji H,Rommel C,Cantley LC,Lane TE,Fruman DA

doi

10.1182/blood-2006-07-038620

subject

Has Abstract

pub_date

2007-04-01 00:00:00

pages

2894-902

issue

7

eissn

0006-4971

issn

1528-0020

pii

blood-2006-07-038620

journal_volume

109

pub_type

杂志文章

相关文献

BLOOD文献大全
  • FERM domain mutations induce gain of function in JAK3 in adult T-cell leukemia/lymphoma.

    abstract::Adult T-cell leukemia/lymphoma (ATLL) is an incurable disease where most patients succumb within the first year of diagnosis. Both standard chemotherapy regimens and mAbs directed against ATLL tumor markers do not alter this aggressive clinical course. Therapeutic development would be facilitated by the discovery of g...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2010-12-319467

    authors: Elliott NE,Cleveland SM,Grann V,Janik J,Waldmann TA,Davé UP

    更新日期:2011-10-06 00:00:00

  • Enhanced production of nitric oxide by bone marrow cells and increased sensitivity to macrophage colony-stimulating factor (CSF) and granulocyte-macrophage CSF after benzene treatment of mice.

    abstract::Nitric oxide is a short-lived reactive mediator that inhibits bone marrow (BM) cell proliferation induced by granulocyte-macrophage colony-stimulating factor (GM-CSF). The present studies show that nitric oxide also inhibits macrophage colony-stimulating factor (M-CSF)-induced growth of mouse BM cells, an effect that ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Punjabi CJ,Laskin JD,Hwang SM,MacEachern L,Laskin DL

    更新日期:1994-06-01 00:00:00

  • Long-term outcome following hematopoietic stem-cell transplantation in Wiskott-Aldrich syndrome: collaborative study of the European Society for Immunodeficiencies and European Group for Blood and Marrow Transplantation.

    abstract::Wiskott-Aldrich syndrome (WAS) is a rare X-linked immunodeficiency with microthrombocytopenia, eczema, recurrent infections, autoimmune disorders, and malignancies that are life-threatening in the majority of patients. In this long-term, retrospective, multicenter study, we analyzed events that occurred in 96 WAS pati...

    journal_title:Blood

    pub_type: 杂志文章,多中心研究

    doi:10.1182/blood-2007-03-076679

    authors: Ozsahin H,Cavazzana-Calvo M,Notarangelo LD,Schulz A,Thrasher AJ,Mazzolari E,Slatter MA,Le Deist F,Blanche S,Veys P,Fasth A,Bredius R,Sedlacek P,Wulffraat N,Ortega J,Heilmann C,O'Meara A,Wachowiak J,Kalwak K,Matthes-

    更新日期:2008-01-01 00:00:00

  • Activation of human granulocytes by arachidonic acid: its use and limitations for investigating granulocyte functions.

    abstract::The effects of arachidonic acid on human granulocytes (polymorphonuclear neutrophil leukocytes, PMN) were examined with respect to early events associated with activation of the superoxide (O2-)-generating system and its reactivation with other stimuli after the addition of fatty acid-free bovine serum albumin. As wit...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Cohen HJ,Chovaniec ME,Takahashi K,Whitin JC

    更新日期:1986-04-01 00:00:00

  • Somatic mutation of bcl-6 genes can occur in the absence of V(H) mutations in chronic lymphocytic leukemia.

    abstract::Somatic mutation in immunoglobulin variable (V) region genes occurs largely in the germinal center and, after neoplastic transformation, imprints V genes of B-cell tumors with the mutational history of the cell of origin. Recently, it has been found that chronic lymphocytic leukemia (CLL) consists of 2 subsets, each w...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Sahota SS,Davis Z,Hamblin TJ,Stevenson FK

    更新日期:2000-06-01 00:00:00

  • Rearrangement of both immunoglobulin and T-cell receptor genes in a prolymphocytic variant of hairy cell leukemia patient resistant to interferon-alpha.

    abstract::We describe a patient with the so-called "prolymphocytic variant" form of hairy cell leukemia (HCL) resistant to treatment with interferon-alpha (IFN-alpha). Analysis of immunoglobulin (Ig) and T-cell receptor-beta (TCR beta) gene rearrangements from serial peripheral blood mononuclear cell specimens (MNCs) confirmed ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Giardina SL,Young HA,Faltynek CR,Jaffe ES,Clark JW,Steis RG,Urba WJ,Mathieson BJ,Gralnick H,Lawrence J

    更新日期:1988-11-01 00:00:00

  • Thrombocytopenia caused by the development of antibodies to thrombopoietin.

    abstract::Thrombocytopenia developed in some individuals treated with a recombinant thrombopoietin (TPO), pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF). Three of the subjects who developed severe thrombocytopenia were analyzed in detail to determine the cause of their thrombocytopenia. Ex...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.v98.12.3241

    authors: Li J,Yang C,Xia Y,Bertino A,Glaspy J,Roberts M,Kuter DJ

    更新日期:2001-12-01 00:00:00

  • Murine prolylcarboxypeptidase depletion induces vascular dysfunction with hypertension and faster arterial thrombosis.

    abstract::Prolylcarboxypeptidase (PRCP) activates prekallikrein to plasma kallikrein, leading to bradykinin liberation, and degrades angiotensin II. We now identify PRCP as a regulator of blood vessel homeostasis. β-Galactosidase staining in PRCP(gt/gt) mice reveals expression in kidney and vasculature. Invasive telemetric moni...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2010-11-318527

    authors: Adams GN,LaRusch GA,Stavrou E,Zhou Y,Nieman MT,Jacobs GH,Cui Y,Lu Y,Jain MK,Mahdi F,Shariat-Madar Z,Okada Y,D'Alecy LG,Schmaier AH

    更新日期:2011-04-07 00:00:00

  • Repurposing a novel anti-cancer RXR agonist to attenuate acute GVHD and maintain graft-versus-leukemia responses.

    abstract::The nuclear receptors (NR) retinoid X receptors (RXRs) exert immunomodulatory functions to control inflammation and metabolism via homodimers and heterodimers with several other NRs including retinoic acid receptors. IRX4204 is a novel, highly specific RXR agonist in clinical trials that potently and selectively activ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.2020005628

    authors: Thangavelu G,Wang C,Loschi M,Saha A,Osborn M,Furlan SN,Aoyama K,McDonald-Hyman C,Aguilar EG,Janesick AS,Chandraratna RA,Refaeli Y,Panoskaltsis-Mortari A,MacDonald KP,Hill GR,Zeiser R,Maillard I,Serody J,Murphy WJ,Mu

    更新日期:2020-09-24 00:00:00

  • Dysregulation of granulocyte, erythrocyte, and NK cell lineages in Fli-1 gene-targeted mice.

    abstract::Targeted disruption of the Friend leukemia integration 1 (Fli-1) proto-oncogene results in severe dysmegakaryopoiesis and embryonic lethality. We used morula-stage aggregation as a strategy to further clarify the hematopoietic defects of the Fli-1 gene-targeted mice. Analyses of lineage expression of Fli-1(+/-) and Fl...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2003-12-4345

    authors: Masuya M,Moussa O,Abe T,Deguchi T,Higuchi T,Ebihara Y,Spyropoulos DD,Watson DK,Ogawa M

    更新日期:2005-01-01 00:00:00

  • A20 protects endothelial cells from TNF-, Fas-, and NK-mediated cell death by inhibiting caspase 8 activation.

    abstract::A20 is a stress response gene in endothelial cells (ECs). A20 serves a dual cytoprotective function, protecting from tumor necrosis factor (TNF)-mediated apoptosis and inhibiting inflammation via blockade of the transcription factor nuclear factor-kappaB (NF-kappaB). In this study, we evaluated the molecular basis of ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2003-02-0635

    authors: Daniel S,Arvelo MB,Patel VI,Longo CR,Shrikhande G,Shukri T,Mahiou J,Sun DW,Mottley C,Grey ST,Ferran C

    更新日期:2004-10-15 00:00:00

  • Animal model of fetal and neonatal immune thrombocytopenia: role of neonatal Fc receptor in the pathogenesis and therapy.

    abstract::Fetal and neonatal immune thrombocytopenia (FNIT) is a severe bleeding disorder in which maternal antibodies cross the placenta and destroy fetal/neonatal platelets. It has been demonstrated that the neonatal Fc receptor (FcRn) regulates immunoglobulin G (IgG) homeostasis and plays an important role in transplacental ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2010-05-284919

    authors: Chen P,Li C,Lang S,Zhu G,Reheman A,Spring CM,Freedman J,Ni H

    更新日期:2010-11-04 00:00:00

  • The impact of low-dose busulfan on clonal dynamics in nonhuman primates.

    abstract::An understanding of the number and contribution of individual pluripotent hematopoietic stem cells (HSCs) to the formation of blood lineages has important clinical implications for gene therapy and stem cell transplantation. We have been able to efficiently mark rhesus macaque long-term repopulating stem and progenito...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2003-08-2935

    authors: Kuramoto K,Follman D,Hematti P,Sellers S,Laukkanen MO,Seggewiss R,Metzger ME,Krouse A,Donahue RE,von Kalle C,Dunbar CE

    更新日期:2004-09-01 00:00:00

  • Dexamethasone augments CXCR4-mediated signaling in resting human T cells via the activation of the Src kinase Lck.

    abstract::Dexamethasone (DM) is a synthetic member of the glucocorticoid (GC) class of hormones that possesses anti-inflammatory and immunosuppressant activity and is commonly used to treat chronic inflammatory disorders, severe allergies, and other disease states. Although GCs are known to mediate well-defined transcriptional ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2008-04-151803

    authors: Ghosh MC,Baatar D,Collins G,Carter A,Indig F,Biragyn A,Taub DD

    更新日期:2009-01-15 00:00:00

  • Tumor necrosis factor induces the production of urokinase-type plasminogen activator by human endothelial cells.

    abstract::Endothelial cells play an important role in the regulation of fibrinolysis by the production of several key regulatory proteins. The cytokines tumor necrosis factor (TNF), lymphotoxin, and interleukin-1 (IL-1), but not interleukin-6, increase the production of plasminogen activator inhibitor-1 (PAI-1) by endothelial c...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: van Hinsbergh VW,van den Berg EA,Fiers W,Dooijewaard G

    更新日期:1990-05-15 00:00:00

  • Presence of functional dendritic cells in patients chronically infected with hepatitis C virus.

    abstract::The absence of expanded numbers of hepatitis C virus (HCV)-reactive CD8(+) T lymphocytes (CTLs) in patients chronically infected with HCV has led to the investigation of dendritic cell (DC) function in this population as a potential cause for this defect. Several studies have shown evidence for impaired monocyte-deriv...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2003-04-1339

    authors: Longman RS,Talal AH,Jacobson IM,Albert ML,Rice CM

    更新日期:2004-02-01 00:00:00

  • Alternatively activated macrophages engage in homotypic and heterotypic interactions through IL-4 and polyamine-induced E-cadherin/catenin complexes.

    abstract::Alternatively activated macrophages (AAMs), triggered by interleukin-4 (IL-4) and IL-13, play a modulating role during Th2 cytokine-driven pathologies, but their molecular armament remains poorly characterized. Here, we established E-cadherin (Cdh1) as a selective marker for IL-4/IL-13-exposed mouse and human macropha...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2009-05-221598

    authors: Van den Bossche J,Bogaert P,van Hengel J,Guérin CJ,Berx G,Movahedi K,Van den Bergh R,Pereira-Fernandes A,Geuns JM,Pircher H,Dorny P,Grooten J,De Baetselier P,Van Ginderachter JA

    更新日期:2009-11-19 00:00:00

  • Evidence for a pretranslational defect in hereditary and acquired myeloperoxidase deficiency.

    abstract::Myeloperoxidase (MPO) is a heme containing enzyme involved in the oxygen-dependent microbicidal activity of human polymorphonuclear leukocytes (PMN). Complete hereditary and acquired MPO deficiencies are defined as lack of peroxidase activity in PMN. Using this criterion, we studied a patient with complete hereditary ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Tobler A,Selsted ME,Miller CW,Johnson KR,Novotny MJ,Rovera G,Koeffler HP

    更新日期:1989-05-15 00:00:00

  • Prognostic significance of Bax protein expression in diffuse aggressive non-Hodgkin's lymphoma.

    abstract::Bax is a proapoptotic member of the Bcl-2 protein family. The incidence and prognostic significance of Bax protein expression in diffuse non-Hodgkin's lymphomas with a large cell component (DLCL) was determined by an immunohistochemical method by using paraffin-embedded tumors from a cohort of patients treated uniform...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Gascoyne RD,Krajewska M,Krajewski S,Connors JM,Reed JC

    更新日期:1997-10-15 00:00:00

  • Functional involvement of RINF, retinoid-inducible nuclear factor (CXXC5), in normal and tumoral human myelopoiesis.

    abstract::Retinoids triggers differentiation of acute promyelocytic leukemia (APL) blasts by transcriptional regulation of myeloid regulatory genes. Using a microarray approach, we have identified a novel retinoid-responsive gene (CXXC5) encoding a nuclear factor, retinoid-inducible nuclear factor (RINF), that contains a CXXC-t...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2008-07-170035

    authors: Pendino F,Nguyen E,Jonassen I,Dysvik B,Azouz A,Lanotte M,Ségal-Bendirdjian E,Lillehaug JR

    更新日期:2009-04-02 00:00:00

  • Hydroxyurea makes inflammation "just right"?

    abstract::Hydroxyurea treatment of sickle cell mice improved their survival from pneumococcal pneumonia, counteracting the abnormally elevated inflammatory response and reducing invasion of bacteria into the bloodstream, through down regulation of E-selectin. ...

    journal_title:Blood

    pub_type: 评论,杂志文章

    doi:10.1182/blood-2011-12-397794

    authors: Hsu LL

    更新日期:2012-02-23 00:00:00

  • CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma.

    abstract::The combination of cyclophosphamide, vincristine, and prednisone (CVP) is one of several standard treatment options for advanced follicular lymphoma. This, like similar chemotherapeutic regimens, induces response rates of 60% to 80%, with a median response duration of under 2 years. Rituximab, a chimeric monoclonal an...

    journal_title:Blood

    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验

    doi:10.1182/blood-2004-08-3175

    authors: Marcus R,Imrie K,Belch A,Cunningham D,Flores E,Catalano J,Solal-Celigny P,Offner F,Walewski J,Raposo J,Jack A,Smith P

    更新日期:2005-02-15 00:00:00

  • Impaired natural killer activity in patients with chronic lymphocytic leukemia is associated with a deficiency of azurophilic cytoplasmic granules in putative NK cells.

    abstract::This study was undertaken to gain further insight into the severely impaired natural killer (NK) activity we and others have previously observed in patients with chronic lymphocytic leukemia (CLL). Normal individuals' NK cells are large granular lymphocytes (LGL) that (A) bind to and lyse NK-sensitive cells, including...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Kay NE,Zarling JM

    更新日期:1984-02-01 00:00:00

  • Isolation and characterization of human antigen-specific TCR alpha beta+ CD4(-)CD8- double-negative regulatory T cells.

    abstract::Down-regulation of immune responses by regulatory T (Treg) cells is an important mechanism involved in the induction of tolerance to allo-antigens (Ags). Recently, a novel subset of Ag-specific T-cell receptor (TCR)alpha beta+ CD4(-)CD8- (double-negative [DN]) Treg cells has been found to be able to prevent the reject...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2004-07-2583

    authors: Fischer K,Voelkl S,Heymann J,Przybylski GK,Mondal K,Laumer M,Kunz-Schughart L,Schmidt CA,Andreesen R,Mackensen A

    更新日期:2005-04-01 00:00:00

  • How targeted therapy disrupts the treatment paradigm for acquired TTP: the risks, benefits, and unknowns.

    abstract::Insights into immune-mediated thrombotic thrombocytopenic purpura (iTTP) pathophysiology have led to novel targeted therapies. Immunomodulatory strategies target anti-ADAMTS13 antibodies: rituximab is effective in inducing responses in refractory/relapsed TTP and increasing relapse-free survival; caplacizumab targets ...

    journal_title:Blood

    pub_type: 杂志文章,评审

    doi:10.1182/blood.2019000954

    authors: Mazepa MA,Masias C,Chaturvedi S

    更新日期:2019-08-01 00:00:00

  • Membrane-bound Fas (Apo-1/CD95) ligand on leukemic cells: A mechanism of tumor immune escape in leukemia patients.

    abstract::There is evidence from bone marrow transplantation that T cells may be involved in the immunologic control of leukemia. But many patients relapse despite a potent graft-versus-leukemia effect mediated by allogeneic T cells. The expression of the FasL protein has been suggested as a mechanism of tumor immune escape. We...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Buzyn A,Petit F,Ostankovitch M,Figueiredo S,Varet B,Guillet JG,Ameisen JC,Estaquier J

    更新日期:1999-11-01 00:00:00

  • Coactivator function of RIP140 for NFkappaB/RelA-dependent cytokine gene expression.

    abstract::Inflammatory responses represent a hallmark of numerous pathologies including sepsis, bacterial infection, insulin resistance, and malign obesity. Here we describe an unexpected coactivator function for the nuclear receptor interacting protein 140 (RIP140) for nuclear factor kappaB (NFkappaB), a master transcriptional...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2007-11-121699

    authors: Zschiedrich I,Hardeland U,Krones-Herzig A,Berriel Diaz M,Vegiopoulos A,Müggenburg J,Sombroek D,Hofmann TG,Zawatzky R,Yu X,Gretz N,Christian M,White R,Parker MG,Herzig S

    更新日期:2008-07-15 00:00:00

  • Characterization and pharmacokinetic parameters of recombinant soluble interleukin-4 receptor.

    abstract::The interleukin-4 receptor (IL-4R) is expressed as a 140-Kd membrane glycoprotein that binds IL-4 with high affinity. Recently, cDNA clones for the murine IL-4R have been isolated. One clone encodes an integral membrane protein, while another encodes a protein in which translation is terminated before the transmembran...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Jacobs CA,Lynch DH,Roux ER,Miller R,Davis B,Widmer MB,Wignall J,VandenBos T,Park LS,Beckmann MP

    更新日期:1991-06-01 00:00:00

  • Pseudo-Bernard-Soulier syndrome: thrombocytopenia caused by autoantibody to platelet glycoprotein Ib.

    abstract::The Bernard-Soulier syndrome is an inherited bleeding disorder that is due to a deficiency in platelet glycoprotein Ib. Bernard-Soulier platelets fail to agglutinate in response to ristocetin despite normal levels of factor VIII:von Willebrand factor. We report a patient who developed severe refractory thrombocytopeni...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Devine DV,Currie MS,Rosse WF,Greenberg CS

    更新日期:1987-08-01 00:00:00

  • HIV-1 Nef drives macrophages into hiding.

    abstract::In this issue of Blood, Vérollet et al show that expression of the HIV-1–derived protein Nef alters the migratory mode adopted by macrophages, enhancing macrophage tissue infiltration and explaining the observed accumulation of tissue-resident macrophages in some HIV-infected patients. ...

    journal_title:Blood

    pub_type: 评论,杂志文章

    doi:10.1182/blood-2015-01-618983

    authors: Morley SC

    更新日期:2015-03-05 00:00:00