0000000000552869

AUTHOR

Ralph M. Steinman

showing 3 related works from this author

Classical Flt3L-dependent dendritic cells control immunity to protein vaccine

2014

DCs are critical for initiating immunity. The current paradigm in vaccine biology is that DCs migrating from peripheral tissue and classical lymphoid-resident DCs (cDCs) cooperate in the draining LNs to initiate priming and proliferation of T cells. Here, we observe subcutaneous immunity is Fms-like tyrosine kinase 3 ligand (Flt3L) dependent. Flt3L is rapidly secreted after immunization; Flt3 deletion reduces T cell responses by 50%. Flt3L enhances global T cell and humoral immunity as well as both the numbers and antigen capture capacity of migratory DCs (migDCs) and LN-resident cDCs. Surprisingly, however, we find immunity is controlled by cDCs and actively tempered in vivo by migDCs. Del…

MaleCellular immunityInjections IntradermalLangerinOvalbuminInjections SubcutaneousT cellImmunologyAntigen presentationGene ExpressionPriming (immunology)Mice Transgenicchemical and pharmacologic phenomenaLigandsInterferon-gammaMice03 medical and health sciences0302 clinical medicineAntigenT-Lymphocyte SubsetsImmunitymedicineAnimalsHumansImmunology and AllergyLectins C-Type030304 developmental biologyMice KnockoutAntigen PresentationVaccines0303 health sciencesbiologyMembrane ProteinsProteinsDendritic Cellsbiochemical phenomena metabolism and nutritionImmunity Humoral3. Good healthMice Inbred C57BLMannose-Binding Lectinsmedicine.anatomical_structureAntigens SurfaceHumoral immunityImmunologybiology.proteinbacteriaFemaleTranscription Factors030215 immunologyJournal of Experimental Medicine
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Efficient Targeting of Protein Antigen to the Dendritic Cell Receptor DEC-205 in the Steady State Leads to Antigen Presentation on Major Histocompati…

2002

To identify endocytic receptors that allow dendritic cells (DCs) to capture and present antigens on major histocompatibility complex (MHC) class I products in vivo, we evaluated DEC-205, which is abundant on DCs in lymphoid tissues. Ovalbumin (OVA) protein, when chemically coupled to monoclonal alphaDEC-205 antibody, was presented by CD11c+ lymph node DCs, but not by CD11c- cells, to OVA-specific, CD4+ and CD8+ T cells. Receptor-mediated presentation was at least 400 times more efficient than unconjugated OVA and, for MHC class I, the DCs had to express transporter of antigenic peptides (TAP) transporters. When alphaDEC-205:OVA was injected subcutaneously, OVA protein was identified over a …

CD8-Positive T-LymphocytesMice0302 clinical medicineImmunology and AllergyCytotoxic T cellMice KnockoutAntigen Presentation0303 health sciencesMembrane GlycoproteinstoleranceAntibodies MonoclonalDEC-205 receptorrespiratory systemFlow CytometryEndocytosismedicine.anatomical_structureMHC class IFemaleOvalbuminT cellImmunologyAntigen presentationReceptors Cell Surfacechemical and pharmacologic phenomenaBiologyMajor histocompatibility complexArticleMinor Histocompatibility Antigens03 medical and health sciencesAntigenAntigens CDMHC class IImmune TolerancemedicineAnimalsLectins C-Typedendritic cellsAntigensCD40 Antigens030304 developmental biologyHistocompatibility Antigens Class IDendritic cellMolecular biologyCD11c AntigenMice Inbred C57BLCD8 T cellbiology.proteinLymph NodesCarrier ProteinsCD8030215 immunologyJournal of Experimental Medicine
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Vaccination with Mage-3a1 Peptide–Pulsed Mature, Monocyte-Derived Dendritic Cells Expands Specific Cytotoxic T Cells and Induces Regression of Some M…

1999

Dendritic cells (DCs) are considered to be promising adjuvants for inducing immunity to cancer. We used mature, monocyte-derived DCs to elicit resistance to malignant melanoma. The DCs were pulsed with Mage-3A1 tumor peptide and a recall antigen, tetanus toxoid or tuberculin. 11 far advanced stage IV melanoma patients, who were progressive despite standard chemotherapy, received five DC vaccinations at 14-d intervals. The first three vaccinations were administered into the skin, 3 × 106 DCs each subcutaneously and intradermally, followed by two intravenous injections of 6 × 106 and 12 × 106 DCs, respectively. Only minor (less than or equal to grade II) side effects were observed. Immunity t…

AdultMaleLung NeoplasmsImmunologyCD8-Positive T-LymphocytesTuberculincytotoxic T lymphocytesCancer VaccinesMonocytesLymphocytes Tumor-InfiltratingImmune systemAntigenAntigens NeoplasmTetanus ToxoidmelanomaHumansImmunology and AllergyMedicineCytotoxic T celldendritic cellsNeoplasm MetastasisLymph nodeImmunization ScheduleAgedNeoplasm Stagingactive immunotherapybusiness.industryMelanomaDendritic cellMiddle Agedvaccinationmedicine.diseaseTumor antigenNeoplasm Proteinsmedicine.anatomical_structureImmunologyFemaleOriginal ArticlebusinessCD8T-Lymphocytes CytotoxicJournal of Experimental Medicine
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