2013
Host-derived CD8+ dendritic cells are required for induction of optimal graft-versus-tumor responses after experimental allogeneic bone marrow transplantation
Toubai T, Sun Y, Luker G, Liu J, Luker K, Tawara I, Evers R, Liu C, Mathewson N, Malter C, Nieves E, Choi S, Murphy K, Reddy P. Host-derived CD8+ dendritic cells are required for induction of optimal graft-versus-tumor responses after experimental allogeneic bone marrow transplantation. Blood 2013, 121: 4231-4241. PMID: 23520337, PMCID: PMC3656455, DOI: 10.1182/blood-2012-05-432872.Peer-Reviewed Original ResearchConceptsAntigen-presenting cellsTumor-specific antigensGVT responseAllo-HCTAPC subsetsDendritic cellsExperimental allogeneic bone marrow transplantationHost-derived antigen-presenting cellsAllogeneic bone marrow transplantationAllogeneic hematopoietic cell transplantationAlloantigen-specific responsesHost-derived CD8Donor T cellsHematopoietic cell transplantationBone marrow transplantationRelevant murine modelStimulation of TLR3Host diseaseTumor effectMarrow transplantationCell transplantationTumor responseSerious toxicityT cellsOptimal graft
2011
Induction of acute GVHD by sex-mismatched H-Y antigens in the absence of functional radiosensitive host hematopoietic–derived antigen-presenting cells
Toubai T, Tawara I, Sun Y, Liu C, Nieves E, Evers R, Friedman T, Korngold R, Reddy P. Induction of acute GVHD by sex-mismatched H-Y antigens in the absence of functional radiosensitive host hematopoietic–derived antigen-presenting cells. Blood 2011, 119: 3844-3853. PMID: 22101894, PMCID: PMC3335388, DOI: 10.1182/blood-2011-10-384057.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAnimalsAntigen-Presenting CellsBone Marrow TransplantationCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCells, CulturedDendritic CellsEndothelial CellsFemaleGraft vs Host DiseaseHematopoiesisHistocompatibilityH-Y AntigenIsoantigensMaleMiceMice, Inbred BALB CMice, Inbred C57BLMice, Mutant StrainsRadiation ToleranceThymectomyConceptsAcute GVHDT cellsAg presentationAlloreactive donor T cellsAllogeneic BM transplantationDonor T cellsMinor histocompatibility AgAntigen-presenting cellsGvH responseGVHD lethalityBM transplantationHistocompatibility AgClinical dataGVHDY antigenAPCY AgPresentationCellsTransplantationAbsenceInfusionAntigenRecipientsHost Basophils Are Dispensable for Induction of Donor T Helper 2 Cell Differentiation and Severity of Experimental Graft-versus-Host Disease
Tawara I, Nieves E, Liu C, Evers R, Toubai T, Sun Y, Alrubaie M, Reddy P. Host Basophils Are Dispensable for Induction of Donor T Helper 2 Cell Differentiation and Severity of Experimental Graft-versus-Host Disease. Transplantation And Cellular Therapy 2011, 17: 1747-1753. PMID: 21871863, PMCID: PMC3220796, DOI: 10.1016/j.bbmt.2011.08.013.Peer-Reviewed Original ResearchConceptsAntigen-presenting cellsAllogeneic bone marrow transplantationSeverity of GVHDBone marrow transplantationHost diseaseTh2 responsesMarrow transplantationDonor T cell proliferationDonor T-cell responsesInduction of graftT cell responsesT cell proliferationT helper 2 (Th2) cell differentiationTh2 polarizationLymphocyte responsesExperimental graftGVHDCell responsesBasophilsCell proliferationSeverityTransplantationGraftRecent dataDiseaseCeacam1 Separates Graft-versus-Host-Disease from Graft-versus-Tumor Activity after Experimental Allogeneic Bone Marrow Transplantation
Lu S, Kappel L, Charbonneau-Allard A, Atallah R, Holland A, Turbide C, Hubbard V, Rotolo J, Smith M, Suh D, King C, Rao U, Yim N, Bautista J, Jenq R, Penack O, Na I, Liu C, Murphy G, Alpdogan O, Blumberg R, Macian F, Holmes K, Beauchemin N, van den Brink M. Ceacam1 Separates Graft-versus-Host-Disease from Graft-versus-Tumor Activity after Experimental Allogeneic Bone Marrow Transplantation. PLOS ONE 2011, 6: e21611. PMID: 21760897, PMCID: PMC3130781, DOI: 10.1371/journal.pone.0021611.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone Marrow TransplantationCarcinoembryonic AntigenCD8-Positive T-LymphocytesCell PolarityCell ProliferationCytotoxicity, ImmunologicDendritic CellsGraft vs Host DiseaseGraft vs Tumor EffectHumansIntegrinsIntestine, SmallLymphocyte ActivationLymphocyte CountLymphoid TissueMiceOrgan SpecificityRadiation Injuries, ExperimentalRadiation, IonizingTransplantation, HomologousConceptsAllogeneic bone marrow transplantationBone marrow transplantationDonor T cellsCD8 T cellsT cellsMarrow transplantationGVHD mortalityTumor activityExperimental allogeneic bone marrow transplantationInflammatory bowel disease modelCell adhesion molecule-1GVHD target tissuesRegulation of GVHDTarget tissuesT cell numbersAlloreactive T cellsAdhesion molecule-1T cell activationVariety of physiologicAllo-BMTSystemic GVHDHost diseaseSmall intestinal cryptsDonor graftsAllogeneic transplantationIkaros-Notch axis in host hematopoietic cells regulates experimental graft-versus-host disease
Toubai T, Sun Y, Tawara I, Friedman A, Liu C, Evers R, Nieves E, Malter C, Chockley P, Maillard I, Winandy S, Reddy P. Ikaros-Notch axis in host hematopoietic cells regulates experimental graft-versus-host disease. Blood 2011, 118: 192-204. PMID: 21471527, PMCID: PMC3139384, DOI: 10.1182/blood-2010-12-324616.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigen-Presenting CellsCD8-Positive T-LymphocytesCells, CulturedDendritic CellsDisease Models, AnimalFemaleGraft vs Host DiseaseHematopoiesisIkaros Transcription FactorImmunophenotypingMaleMiceMice, Inbred BALB CMice, Inbred C3HMice, Inbred C57BLMice, Mutant StrainsReceptor, Notch1Signal TransductionConceptsDendritic cellsAcute GVHDDonor T cell expansionExperimental bone marrow transplantationHost hematopoietic cellsInduction of GVHDAllogeneic T cellsBone marrow transplantationT cell expansionRelevant murine modelGvH responseAllostimulatory capacityHost diseaseWild-type controlsDC biologyMarrow transplantationPotent APCsActivation markersTLR stimulationT cellsMurine modelGVHDExperimental graftEnhanced stimulationIkaros deficiency
2009
Hepatitis C virus modulates human monocyte‐derived dendritic cells
Eksioglu E, Bess J, Zhu H, Xu Y, Dong H, Elyar J, Nelson D, Liu C. Hepatitis C virus modulates human monocyte‐derived dendritic cells. Journal Of Viral Hepatitis 2009, 17: 757-769. PMID: 20051006, PMCID: PMC3731759, DOI: 10.1111/j.1365-2893.2009.01231.x.Peer-Reviewed Original ResearchConceptsHepatitis C virusNewcastle disease virusHCV infectionC virusHuman monocyte-derived dendritic cellsViral titresMonocyte-derived dendritic cellsType 1 IFN responseFlow cytometryType 1 interferon responseMaturation of DCsDendritic cell responsesReal-time reverse transcriptase-polymerase chain reactionReverse transcriptase-polymerase chain reactionTranscriptase-polymerase chain reactionHuh-7.5 cellsDC numbersDendritic cellsImmature DCsIFNβ expressionJFH-1Control monocytesHost immunityViral evasionIFN responseImmunization with host-type CD8α+ dendritic cells reduces experimental acute GVHD in an IL-10–dependent manner
Toubai T, Malter C, Tawara I, Liu C, Nieves E, Lowler K, Sun Y, Reddy P. Immunization with host-type CD8α+ dendritic cells reduces experimental acute GVHD in an IL-10–dependent manner. Blood 2009, 115: 724-735. PMID: 19965670, PMCID: PMC2810989, DOI: 10.1182/blood-2009-06-229708.Peer-Reviewed Original ResearchConceptsT cell responsesDendritic cellsT cellsImmune responseUndesirable immune responsesIL-10Major histocompatibilityDonor T-cell responsesIL-10-dependent mannerExperimental acute GVHDImmunization of donorsDonor T cellsAntigen-specific mannerB6 modelBALB/c T cellsCertain immune responsesBALB/cAcute GVHDHost diseaseInterleukin-10Active immunizationInflammatory cytokinesVaccination strategiesAntigen specificityGVHD
2008
Histone deacetylase inhibition modulates indoleamine 2,3-dioxygenase–dependent DC functions and regulates experimental graft-versus-host disease in mice
Reddy P, Sun Y, Toubai T, Duran-Struuck R, Clouthier S, Weisiger E, Maeda Y, Tawara I, Krijanovski O, Gatza E, Liu C, Malter C, Mascagni P, Dinarello C, Ferrara J. Histone deacetylase inhibition modulates indoleamine 2,3-dioxygenase–dependent DC functions and regulates experimental graft-versus-host disease in mice. Journal Of Clinical Investigation 2008, 118: 2562-2573. PMID: 18568076, PMCID: PMC2430497, DOI: 10.1172/jci34712.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDBone Marrow TransplantationCytokinesDendritic CellsEnzyme InhibitorsFemaleGene ExpressionGraft vs Host DiseaseHistone Deacetylase InhibitorsHumansHydroxamic AcidsIndoleamine-Pyrrole 2,3,-DioxygenaseLipopolysaccharidesLymphocyte ActivationMiceMice, Inbred BALB CMice, Inbred C3HMice, Inbred C57BLMice, Inbred StrainsMice, KnockoutRNA, Small InterferingSurvival AnalysisT-LymphocytesVorinostatConceptsDC functionHDAC inhibitorsSuberoylanilide hydroxamic acidHost diseaseExperimental graftBlockade of IDOPretreatment of DCsAllogeneic BM transplantationBM-derived cellsImmune-mediated diseasesExpression of CD40Expression of indoleamineBM transplantation modelExposure of DCsInduction of IDOVivo functional roleHistone deacetylase inhibitionHistone deacetylase inhibitorsMechanism of actionProinflammatory cytokinesBM transplantationWT DCsTransplantation modelImmunomodulatory functionsDeacetylase inhibitionOrgan-derived dendritic cells have differential effects on alloreactive T cells
Kim T, Terwey T, Zakrzewski J, Suh D, Kochman A, Chen M, King C, Borsotti C, Grubin J, Smith O, Heller G, Liu C, Murphy G, Alpdogan O, van den Brink M. Organ-derived dendritic cells have differential effects on alloreactive T cells. Blood 2008, 111: 2929-2940. PMID: 18178870, PMCID: PMC2254543, DOI: 10.1182/blood-2007-06-096602.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell ProliferationDendritic CellsGene Expression ProfilingGraft vs Host DiseaseHumansIntegrinsIsoantigensLigandsLipopolysaccharidesLiverLymphocyte ActivationMiceMice, Inbred BALB CMice, Inbred C57BLOligonucleotide Array Sequence AnalysisOrgan SpecificityPhenotypeReceptors, Lymphocyte HomingSelectinsSurvival RateT-LymphocytesUp-RegulationConceptsAlloreactive T cellsBone marrow transplantationDendritic cellsT cellsGVHD mortalityLymph nodesAlloreactive donor T cellsGut-draining lymph nodesLiver-derived dendritic cellsNaive allogeneic T cellsMurine bone marrow transplantationPathophysiology of GVHDTarget organ liverDonor T cellsInduction of graftAllogeneic T cellsPeripheral lymph nodesGut-homing phenotypeMurine BMT modelHost diseaseAdoptive transferHoming moleculesMarrow transplantationStimulatory capacityBMT model
2007
A Novel Role for the Semaphorin Sema4D in the Induction of Allo-responses
Duran-Struuck R, Tawara I, Lowler K, Clouthier S, Weisiger E, Rogers C, Luker G, Kumanogoh A, Liu C, Ferrara J, Reddy P. A Novel Role for the Semaphorin Sema4D in the Induction of Allo-responses. Transplantation And Cellular Therapy 2007, 13: 1294.e1-1294.e11. PMID: 17950916, PMCID: PMC2278022, DOI: 10.1016/j.bbmt.2007.07.014.Peer-Reviewed Original ResearchConceptsBone marrow transplantT cellsWT T cellsDendritic cellsBALB/c recipient miceIntrinsic T cell defectPreservation of GVLAllo-immune responsesLess TNF-alphaTumor-free survivalT cell defectsAntigen presenting cellsWild-type T cellsCertain immune responsesP815 murine mastocytoma cell lineT cell-APC interactionsFree survivalHost diseaseIL-12p70Leukemia responseOrgan damageSema4D expressionMarrow transplantCytotoxic functionSyngeneic recipients
2006
An effective cancer vaccine modality: Lentiviral modification of dendritic cells expressing multiple cancer-specific antigens
Wang B, He J, Liu C, Chang L. An effective cancer vaccine modality: Lentiviral modification of dendritic cells expressing multiple cancer-specific antigens. Vaccine 2006, 24: 3477-3489. PMID: 16530303, PMCID: PMC1850619, DOI: 10.1016/j.vaccine.2006.02.025.Peer-Reviewed Original ResearchConceptsTumor-associated antigensDendritic cellsModification of DCsMultiple tumor-associated antigensStrong anti-tumor responsesReactive dendritic cellsAnti-tumor responseT cell responsesLentiviral vectorsCancer-specific antigensCell antigen 2Tumor-bearing miceThymidine kinase suicide geneDC vaccinesVaccine modalitiesCancer immunotherapyCancer patientsTherapeutic injectionsTherapeutic effectExtended survivalAntigen 2Danger signalsVivo eliminationCell responsesTherapeutic potential
2005
Critical role of host γδ T cells in experimental acute graft-versus-host disease
Maeda Y, Reddy P, Lowler K, Liu C, Bishop D, Ferrara J. Critical role of host γδ T cells in experimental acute graft-versus-host disease. Blood 2005, 106: 749-755. PMID: 15797996, PMCID: PMC1895173, DOI: 10.1182/blood-2004-10-4087.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAdoptive TransferAnimalsBone Marrow TransplantationCD40 LigandCell AdhesionCell CommunicationDendritic CellsFemaleGraft vs Host DiseaseInterferon-gammaMiceMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutReceptors, Antigen, T-Cell, gamma-deltaT-Lymphocyte SubsetsTransplantation, HomologousTumor Necrosis Factor-alphaConceptsGammadelta T cellsDendritic cellsT cellsHost diseaseAllostimulatory capacityAllogeneic bone marrow transplantation modelAllogeneic T cell proliferationDonor T cell expansionWild-type B6 recipientsHost antigen-presenting cellsTumor necrosis factor alphaExperimental acute graftWT dendritic cellsNormal dendritic cellsBone marrow transplantation modelBM transplant recipientsΓδ T cellsT cell expansionAntigen-presenting cellsNecrosis factor alphaT cell proliferationAcute graftAcute GVHDB6 recipientsGVHD mortality
2004
Host Dendritic Cells Alone Are Sufficient to Initiate Acute Graft-versus-Host Disease
Duffner U, Maeda Y, Cooke K, Reddy P, Ordemann R, Liu C, Ferrara J, Teshima T. Host Dendritic Cells Alone Are Sufficient to Initiate Acute Graft-versus-Host Disease. The Journal Of Immunology 2004, 172: 7393-7398. PMID: 15187116, DOI: 10.4049/jimmunol.172.12.7393.Peer-Reviewed Original ResearchConceptsHost dendritic cellsDendritic cellsB cellsT cellsAcute GVHDHost diseaseHost-derived dendritic cellsLethal acute GVHDAllogeneic dendritic cellsII-deficient miceMHC class IIMHC class IAcute graftChimeric recipientsHost APCsAPC subsetsAlloantigen expressionGVHDMHC classClass IIClass IRobust proliferationSelective targetingGraftDisease
2003
Impaired thymic negative selection causes autoimmune graft-versus-host disease
Teshima T, Reddy P, Liu C, Williams D, Cooke K, Ferrara J. Impaired thymic negative selection causes autoimmune graft-versus-host disease. Blood 2003, 102: 429-435. PMID: 12663438, DOI: 10.1182/blood-2003-01-0266.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsAutoimmune DiseasesBone Marrow TransplantationCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCells, CulturedClonal DeletionDendritic CellsEpithelial CellsFemaleGraft vs Host DiseaseInflammation MediatorsInterleukin-1MiceMice, Inbred C57BLRadiation ChimeraRadiation ToleranceSelf ToleranceSkinSpleenThymectomyThymus GlandT-Lymphocyte SubsetsTumor Necrosis Factor-alphaVisceraConceptsThymic negative selectionSystemic autoimmune diseaseAntigen-presenting cellsAutoimmune diseasesHost diseaseT cellsAutoreactive T cell repertoireClass IIThymic antigen-presenting cellsMajor histocompatibility complex class IIHistocompatibility complex class IIImpaired negative selectionLethal autoimmune diseaseBone marrow chimerasPeripheral regulatory mechanismsT cell repertoireMHC class IIMHC class INegative selectionAcute graftAcute GVHDAutoimmune graftPeripheral CD4Adoptive transferNaive mice
2002
Flt3 ligand therapy for recipients of allogeneic bone marrow transplants expands host CD8α+ dendritic cells and reduces experimental acute graft-versus-host disease
Teshima T, Reddy P, Lowler K, KuKuruga M, Liu C, Cooke K, Ferrara J. Flt3 ligand therapy for recipients of allogeneic bone marrow transplants expands host CD8α+ dendritic cells and reduces experimental acute graft-versus-host disease. Blood 2002, 99: 1825-1832. PMID: 11861301, DOI: 10.1182/blood.v99.5.1825.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAdjuvants, ImmunologicAnimalsBone Marrow TransplantationCD8 AntigensCell DivisionCoculture TechniquesDendritic CellsDisease Models, AnimalFemaleGraft vs Host DiseaseLymphocyte ActivationMembrane ProteinsMiceMice, Inbred C57BLSurvival RateT-LymphocytesTransplantation, HomologousConceptsDendritic cellsT cell responsesAcute graftHost diseaseDonor T-cell responsesAllogeneic bone marrow transplantationAllogeneic T-cell responsesAllogeneic bone marrow transplantExperimental acute graftHost dendritic cellsPoor stimulatory capacityNormal dendritic cellsAllogeneic T cellsBone marrow transplantationTreatment of miceBone marrow transplantFL treatmentAcute GVHDGVHD mortalityDC subsetsAllogeneic lymphocytesDC numbersMarrow transplantationLigand therapyMarrow transplant