Vaccine-delivered HIV envelope inhibits CD4(+) T-cell activation, a mechanism for poor HIV vaccine responses.


:The human immunodeficiency virus (HIV) causes impairment of the immune system in part by targeting CD4(+) T cells for infection and dysfunction. HIV envelope (Env) present on free virions and infected cells causes dysfunction of uninfected bystander CD4(+) T cells via interaction with both CD4 and coreceptors. Env is commonly used as part of a cocktail of HIV antigens in current vaccines. In DNA and viral vector vaccine approaches, antigen-presenting cells (APCs) and non-APCs in the vicinity of the vaccine delivery site and draining lymph node express vaccine-derived antigens. The studies here demonstrate that cell-surface expression of Env on APCs and non-APCs as part of the vaccine action causes an inhibition of antigen-induced CD4(+) T-cell activation and proliferation mediated by CD4 binding and suggests a potential mechanism for reduced activity of Env-containing HIV vaccines. Similar studies using a functional Env lacking CD4 binding circumvented suppression, suggesting an alternative and potentially superior approach to HIV vaccine design.






Fernando K,Hu H,Ni H,Hoxie JA,Weissman D




Has Abstract


2007-03-15 00:00:00
















  • The human anti-CD30 antibody 5F11 shows in vitro and in vivo activity against malignant lymphoma.

    abstract::CD30 is a promising target for antibody-based immunotherapy of Hodgkin lymphoma (HL) and anaplastic large cell lymphoma. To overcome the limitations from currently available murine anti-CD30 monoclonal antibodies (mAbs), a new fully human anti-CD30 antibody was generated. Binding properties were evaluated by recombina...


    pub_type: 杂志文章


    authors: Borchmann P,Treml JF,Hansen H,Gottstein C,Schnell R,Staak O,Zhang HF,Davis T,Keler T,Diehl V,Graziano RF,Engert A

    更新日期:2003-11-15 00:00:00

  • In pediatric patients, age has more impact on dosing of vitamin K antagonists than VKORC1 or CYP2C9 genotypes.

    abstract::Anticoagulation with vitamin K antagonists (VKAs) is problematic because of difficulties in safely managing dosing. Polymorphisms in cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase genes (VKORC1) have been shown to affect VKA dosing in adults. The association of these polymorphisms on VKA dosing in childr...


    pub_type: 杂志文章


    authors: Nowak-Göttl U,Dietrich K,Schaffranek D,Eldin NS,Yasui Y,Geisen C,Mitchell LG

    更新日期:2010-12-23 00:00:00

  • Regulation of proplatelet formation and platelet release by integrin alpha IIb beta3.

    abstract::Mature megakaryocytes form structures called proplatelets that serve as conduits for platelet packaging and release at vascular sinusoids. Since the megakaryocyte expresses abundant levels of integrin alpha IIb beta3, we have examined a role for fibrinogen in proplatelet development and platelet release alongside that...


    pub_type: 杂志文章


    authors: Larson MK,Watson SP

    更新日期:2006-09-01 00:00:00

  • Tandem autologous stem cell transplantation in high-risk de novo multiple myeloma: final results of the prospective and randomized IFM 99-04 protocol.

    abstract::The combination of high levels of beta2-microglobulin (beta2-m) and chromosome 13 deletion allows identification of a high-risk subgroup of patients with de novo multiple myeloma (MM). In this population of patients, we have evaluated the impact of a murine anti-interleukin 6 (anti-IL-6) monoclonal antibody (BE-8) as ...


    pub_type: 杂志文章,多中心研究,随机对照试验


    authors: Moreau P,Hullin C,Garban F,Yakoub-Agha I,Benboubker L,Attal M,Marit G,Fuzibet JG,Doyen C,Voillat L,Berthou C,Ketterer N,Casassus P,Monconduit M,Michallet M,Najman A,Sotto JJ,Bataille R,Harousseau JL,Intergroupe Fran

    更新日期:2006-01-01 00:00:00

  • Reversion of epigenetically mediated BIM silencing overcomes chemoresistance in Burkitt lymphoma.

    abstract::In Burkitt lymphoma/leukemia (BL), achievement of complete remission with first-line chemotherapy remains a challenging issue, as most patients who respond remain disease-free, whereas those refractory have few options of being rescued with salvage therapies. The mechanisms underlying BL chemoresistance and how it can...


    pub_type: 杂志文章


    authors: Richter-Larrea JA,Robles EF,Fresquet V,Beltran E,Rullan AJ,Agirre X,Calasanz MJ,Panizo C,Richter JA,Hernandez JM,Roman-Gomez J,Prosper F,Martinez-Climent JA

    更新日期:2010-10-07 00:00:00

  • Requirement of alpha and beta subunit transmembrane helix separation for integrin outside-in signaling.

    abstract::Adhesion to extracellular ligands through integrins regulates cell shape, migration, growth, and survival. How integrins transmit signals in the outside-to-in direction remains unknown. Whereas in resting integrins the alpha and beta subunit transmembrane domains are associated, ligand binding promotes dissociation an...


    pub_type: 杂志文章


    authors: Zhu J,Carman CV,Kim M,Shimaoka M,Springer TA,Luo BH

    更新日期:2007-10-01 00:00:00

  • Synthetic anti-BR3 antibodies that mimic BAFF binding and target both human and murine B cells.

    abstract::BR3, which is expressed on all mature B cells, is a specific receptor for the B-cell survival and maturation factor BAFF (B-cell-activating factor belonging to the tumor necrosis factor [TNF] family). In order to investigate the consequences of targeting BR3 in murine models and to assess the potential of BR3 antibodi...


    pub_type: 杂志文章


    authors: Lee CV,Hymowitz SG,Wallweber HJ,Gordon NC,Billeci KL,Tsai SP,Compaan DM,Yin J,Gong Q,Kelley RF,DeForge LE,Martin F,Starovasnik MA,Fuh G

    更新日期:2006-11-01 00:00:00

  • Hematopoietic cell-derived microparticle tissue factor contributes to fibrin formation during thrombus propagation.

    abstract::Tissue factor (TF) is expressed on nonvascular cells and cells within the vessel wall and circulates in blood associated with microparticles. Although blood-borne TF accumulates into the developing thrombus during thrombus formation, the contribution of blood-borne TF and vessel wall TF to thrombin generation in vivo ...


    pub_type: 杂志文章


    authors: Chou J,Mackman N,Merrill-Skoloff G,Pedersen B,Furie BC,Furie B

    更新日期:2004-11-15 00:00:00

  • Immunologic stimulation of early murine hematopoiesis and its abrogation by cyclosporin A.

    abstract::Mice injected chronically with antiplatelet serum develop an increase in the number of megakaryocytic progenitor cells compared to animals given normal rabbit serum. To examine the specificity of this response, progenitor cells giving rise to megakaryocyte, granulocyte-macrophage, erythroid, and mixed-cell colonies we...


    pub_type: 杂志文章


    authors: Burstein SA,Erb SK,Adamson JW,Harker LA

    更新日期:1982-04-01 00:00:00

  • Randomized comparison of double induction and timed-sequential induction to a "3 + 7" induction in adults with AML: long-term analysis of the Acute Leukemia French Association (ALFA) 9000 study.

    abstract::Between 1990 and 1996, we conducted a randomized trial in adults with newly diagnosed acute myeloid leukemia (AML) in order to compare relapse-free interval (RFI) after double induction (arm B), timed-sequential induction (arm C), or control "3 + 7" induction (arm A). Patients achieving complete remission (CR) after i...


    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Castaigne S,Chevret S,Archimbaud E,Fenaux P,Bordessoule D,Tilly H,de Revel T,Simon M,Dupriez B,Renoux M,Janvier M,Micléa JM,Thomas X,Bastard C,Preudhomme C,Bauters F,Degos L,Dombret H

    更新日期:2004-10-15 00:00:00

  • Establishment and phenotypic characterization of three new human myeloma cell lines (U-1957, U-1958, and U-1996).

    abstract::Three new human myeloma cell lines (U-1957, U-1958, and U-1996) have been established in vitro. The cell lines are Epstein-Barr virus (EBV) negative, monoclonal, and aneuploid and should thus represent malignant cell populations and not EBV-carrying non-neoplastic B lymphoblastoid cell lines. The myeloma origin of the...


    pub_type: 杂志文章


    authors: Jernberg H,Nilsson K,Zech L,Lutz D,Nowotny H,Scheirer W

    更新日期:1987-06-01 00:00:00

  • Notch ligands Delta 1 and Jagged1 transmit distinct signals to T-cell precursors.

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    pub_type: 杂志文章


    authors: Lehar SM,Dooley J,Farr AG,Bevan MJ

    更新日期:2005-02-15 00:00:00

  • Circulating IL-15 exists as heterodimeric complex with soluble IL-15Rα in human and mouse serum.

    abstract::IL-15 is an important cytokine for the function of the immune system, but the form(s) of IL-15 produced in the human body are not fully characterized. Coexpression of the single-chain IL-15 and the IL-15 receptor alpha (IL-15Rα) in the same cell allows for efficient production, surface display, and eventual cleavage a...


    pub_type: 杂志文章


    authors: Bergamaschi C,Bear J,Rosati M,Beach RK,Alicea C,Sowder R,Chertova E,Rosenberg SA,Felber BK,Pavlakis GN

    更新日期:2012-07-05 00:00:00

  • Azacitidine with or without eltrombopag for first-line treatment of intermediate- or high-risk MDS with thrombocytopenia.

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    pub_type: 杂志文章,多中心研究,随机对照试验


    authors: Dickinson M,Cherif H,Fenaux P,Mittelman M,Verma A,Portella MSO,Burgess P,Ramos PM,Choi J,Platzbecker U,SUPPORT study investigators.

    更新日期:2018-12-20 00:00:00

  • Sorafenib treatment of FLT3-ITD(+) acute myeloid leukemia: favorable initial outcome and mechanisms of subsequent nonresponsiveness associated with the emergence of a D835 mutation.

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    pub_type: 临床试验,杂志文章


    authors: Man CH,Fung TK,Ho C,Han HH,Chow HC,Ma AC,Choi WW,Lok S,Cheung AM,Eaves C,Kwong YL,Leung AY

    更新日期:2012-05-31 00:00:00

  • Accelerated telomere shortening in glycosylphosphatidylinositol (GPI)-negative compared with GPI-positive granulocytes from patients with paroxysmal nocturnal hemoglobinuria (PNH) detected by proaerolysin flow-FISH.

    abstract::Telomere length has been linked to disease stage and degree of (pan-)cytopenia in patients with bone marrow failure syndromes. The aim of the current study was to analyze the impact of replicative stress on telomere length in residual glycosylphosphatidylinositol-positive (GPI+) versus GPI- hematopoiesis in patients w...


    pub_type: 杂志文章


    authors: Beier F,Balabanov S,Buckley T,Dietz K,Hartmann U,Rojewski M,Kanz L,Schrezenmeier H,Brümmendorf TH

    更新日期:2005-07-15 00:00:00

  • Identification of the soluble granulocyte-macrophage colony stimulating factor receptor protein in vivo.

    abstract::On the basis of the finding of alternatively spliced mRNAs, the alpha-subunit of the receptor for GM-CSF is thought to exist in both a membrane spanning (tmGMRalpha) and a soluble form (solGMRalpha). However, only limited data has been available to support that the solGMRalpha protein product exists in vivo. We hypoth...


    pub_type: 杂志文章


    authors: Sayani F,Montero-Julian FA,Ranchin V,Prevost JM,Flavetta S,Zhu W,Woodman RC,Brailly H,Brown CB

    更新日期:2000-01-15 00:00:00

  • Murine stromal cells counteract the loss of long-term culture-initiating cell potential induced by cytokines in CD34(+)CD38(low/neg) human bone marrow cells.

    abstract::Evidence has been provided recently that shows that high concentrations of cytokines can fulfill functions previously attributed to stromal cells, such as promote the survival of, and led to a net increase in human primitive progenitors initiating long-term cultures in vitro (LTC-IC) or engrafting NOD-SCID (nonobese d...


    pub_type: 杂志文章


    authors: Bennaceur-Griscelli A,Tourino C,Izac B,Vainchenker W,Coulombel L

    更新日期:1999-07-15 00:00:00

  • Allogeneic stem cell transplantation for adult Philadelphia chromosome-negative acute lymphocytic leukemia: comparable survival rates but different risk factors between related and unrelated transplantation in first complete remission.

    abstract::To identify factors to improve the outcomes of related and unrelated allogeneic stem cell transplantations (allo-SCT) for Philadelphia chromosome-negative acute lymphocytic leukemia (Ph(-) ALL) in the first complete remission (CR1), we retrospectively analyzed 1139 Ph(-) ALL patients using the registry data, particula...


    pub_type: 杂志文章


    authors: Nishiwaki S,Inamoto Y,Sakamaki H,Kurokawa M,Iida H,Ogawa H,Fukuda T,Ozawa Y,Kobayashi N,Kasai M,Mori T,Iwato K,Yoshida T,Onizuka M,Kawa K,Morishima Y,Suzuki R,Atsuta Y,Miyamura K

    更新日期:2010-11-18 00:00:00

  • A novel role for IL-22R1 as a driver of inflammation.

    abstract::The interleukin (IL)-22R1 chain of the heterodimeric IL-22 receptor is not expressed on normal leukocytes, but this receptor is expressed on T cells from anaplastic lymphoma kinase-positive (ALK(+)) anaplastic large cell lymphoma (ALCL) patients. To investigate the consequences of aberrant expression of this receptor ...


    pub_type: 杂志文章


    authors: Savan R,McFarland AP,Reynolds DA,Feigenbaum L,Ramakrishnan K,Karwan M,Shirota H,Klinman DM,Dunleavy K,Pittaluga S,Anderson SK,Donnelly RP,Wilson WH,Young HA

    更新日期:2011-01-13 00:00:00

  • Human NK cells at early stages of differentiation produce CXCL8 and express CD161 molecule that functions as an activating receptor.

    abstract::Human natural killer (NK) cell development is a step-by-step process characterized by phenotypically identified stages. CD161 is a marker informative of the NK cell lineage commitment, whereas CD56, CD117, and CD94/NKG2A contribute to define discrete differentiation stages. In cells undergoing in vitro differentiation...


    pub_type: 杂志文章


    authors: Montaldo E,Vitale C,Cottalasso F,Conte R,Glatzer T,Ambrosini P,Moretta L,Mingari MC

    更新日期:2012-04-26 00:00:00

  • Concomitant inactivation of Rb and E2f8 in hematopoietic stem cells synergizes to induce severe anemia.

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    pub_type: 杂志文章


    authors: Hu T,Ghazaryan S,Sy C,Wiedmeyer C,Chang V,Wu L

    更新日期:2012-05-10 00:00:00

  • Rabbit and rat platelets do not respond to thrombin receptor peptides that activate human platelets.

    abstract::Human platelets are aggregated and induced to release their granule contents and form thromboxane by peptides as short as 6-amino acid residues (SFLLRN) corresponding to the newly released N-terminus of the thrombin receptor that is cleaved by thrombin. Using washed platelets, we found that these responses to SFLLRN (...


    pub_type: 杂志文章


    authors: Kinlough-Rathbone RL,Rand ML,Packham MA

    更新日期:1993-07-01 00:00:00

  • Depressed in vitro lymphocyte responses to PHA in patients with Hodgkin disease in continuous long remissions.

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    pub_type: 杂志文章


    authors: Case DC Jr,Hansen JA,Corrales E,Young CW,Dupont B,Pinsky CM,Good RA

    更新日期:1977-05-01 00:00:00

  • Nilotinib is associated with a reduced incidence of BCR-ABL mutations vs imatinib in patients with newly diagnosed chronic myeloid leukemia in chronic phase.

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    pub_type: 杂志文章,多中心研究,随机对照试验


    authors: Hochhaus A,Saglio G,Larson RA,Kim DW,Etienne G,Rosti G,De Souza C,Kurokawa M,Kalaycio ME,Hoenekopp A,Fan X,Shou Y,Kantarjian HM,Hughes TP

    更新日期:2013-05-02 00:00:00

  • Natural killer cell receptors: new biology and insights into the graft-versus-leukemia effect.

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    pub_type: 杂志文章,评审


    authors: Farag SS,Fehniger TA,Ruggeri L,Velardi A,Caligiuri MA

    更新日期:2002-09-15 00:00:00

  • Leukocyte trafficking in a mouse model for leukocyte adhesion deficiency II/congenital disorder of glycosylation IIc.

    abstract::Leukocyte adhesion deficiency II (LAD II), also known as congenital disorder of glycosylation IIc (CDG-IIc), is a human disease in which a defective GDP-fucose transporter (SLC35C1) causes developmental defects and an immunodeficiency that is based on the lack of fucosylated selectin ligands. Since the study of in viv...


    pub_type: 杂志文章


    authors: Yakubenia S,Frommhold D,Schölch D,Hellbusch CC,Körner C,Petri B,Jones C,Ipe U,Bixel MG,Krempien R,Sperandio M,Wild MK

    更新日期:2008-08-15 00:00:00

  • Genistein reduces tumor necrosis factor alpha-induced plasminogen activator inhibitor-1 transcription but not urokinase expression in human endothelial cells.

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    pub_type: 杂志文章


    authors: van Hinsbergh VW,Vermeer M,Koolwijk P,Grimbergen J,Kooistra T

    更新日期:1994-11-01 00:00:00

  • MicroRNA regulation of STAT4 protein expression: rapid and sensitive modulation of IL-12 signaling in human natural killer cells.

    abstract::IL-12 exerts several regulatory effects on natural killer (NK) cells by activating IL-12 signaling. IL-12 signaling is tightly auto-regulated to control its onset and termination, with prolonged IL-12 treatment resulting in IL-12 hyporesponsiveness. However, the mechanisms underlying IL-12 auto-regulation are still un...


    pub_type: 杂志文章


    authors: Huang Y,Lei Y,Zhang H,Hou L,Zhang M,Dayton AI

    更新日期:2011-12-22 00:00:00

  • Chronic myelocytic leukemia (CML): failure to detect residual normal committed stem cells in vitro.

    abstract::Granulocytic colonies grown in culture from marrow and peripheral blood from five patients with Ph1-positive CML and heterozygous at the G-6-PD locus were analyzed for G-6-PD in order to identify CFU-C that do not arise from the CML clone. The patients had both B and A enzymes in normal tissues, but their CML clones t...


    pub_type: 杂志文章


    authors: Singer JW,Fialkow PJ,Steinmann L,Najfeld V,Stein SJ,Robinson WA

    更新日期:1979-02-01 00:00:00