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 dataDiseasePretransplant CSF-1 therapy expands recipient macrophages and ameliorates GVHD after allogeneic hematopoietic cell transplantation
Hashimoto D, Chow A, Greter M, Saenger Y, Kwan W, Leboeuf M, Ginhoux F, Ochando J, Kunisaki Y, van Rooijen N, Liu C, Teshima T, Heeger P, Stanley E, Frenette P, Merad M. Pretransplant CSF-1 therapy expands recipient macrophages and ameliorates GVHD after allogeneic hematopoietic cell transplantation. Journal Of Experimental Medicine 2011, 208: 1069-1082. PMID: 21536742, PMCID: PMC3092347, DOI: 10.1084/jem.20101709.Peer-Reviewed Original ResearchConceptsDonor allogeneic T cellsDonor T cell expansionAllogeneic hematopoietic cell transplantationAllogeneic T cellsHematopoietic cell transplantationAllo-HCTT cell expansionT cellsAcute GVHDCell transplantationHost macrophagesHost antigen-presenting cellsMacrophage poolPotential prophylactic therapyAlloreactive T cellsAntigen-presenting cellsAcute graftGVHD morbidityGVHD mortalityHost DCsHost diseaseProphylactic therapyRecipient miceGVHDRecipient macrophages
2010
Secondary Lymphoid Organs Contribute to, but Are Not Required for the Induction of Graft-versus-Host Responses following Allogeneic Bone Marrow Transplantation: A shifting Paradigm for T Cell Allo-activation
Silva I, Olkiewicz K, Askew D, Fisher J, Chaudhary M, Vannella K, Deurloo D, Choi S, Pierce E, Clouthier S, Liu C, Cooke K. Secondary Lymphoid Organs Contribute to, but Are Not Required for the Induction of Graft-versus-Host Responses following Allogeneic Bone Marrow Transplantation: A shifting Paradigm for T Cell Allo-activation. Transplantation And Cellular Therapy 2010, 16: 598-611. PMID: 20117226, PMCID: PMC3838892, DOI: 10.1016/j.bbmt.2009.12.007.Peer-Reviewed Original ResearchConceptsSecondary lymphoid organsDonor T cellsAllogeneic bone marrow transplantationAly/aly miceBone marrow transplantationAntigen-presenting cellsPeyer's patchesT cellsAllo-BMTLymph nodesMarrow transplantationAly miceLymphoid organsAllogeneic T-cell responsesHost antigen-presenting cellsInduction of GVHDInduction of graftT cell responsesT cell activationDisparate donorsHost diseaseBMT recipientsMajor complicationsTumor burdenLeukemia activity
2009
NOD2 regulates hematopoietic cell function during graft-versus-host disease
Penack O, Smith O, Cunningham-Bussel A, Liu X, Rao U, Yim N, Na I, Holland A, Ghosh A, Lu S, Jenq R, Liu C, Murphy G, Brandl K, van den Brink M. NOD2 regulates hematopoietic cell function during graft-versus-host disease. Journal Of Experimental Medicine 2009, 206: 2101-2110. PMID: 19737867, PMCID: PMC2757869, DOI: 10.1084/jem.20090623.Peer-Reviewed Original ResearchConceptsAntigen-presenting cellsNOD2 deficiencyHost diseaseCrohn's diseaseExperimental allogeneic bone marrow transplantationAllogeneic bone marrow transplantationHost antigen-presenting cellsAllo-BMT recipientsDevelopment of GVHDExperimental colitis modelHematopoietic cellsHost hematopoietic cellsDonor T cellsIndependent risk factorBone marrow chimerasBone marrow transplantationChimeric recipientsIntestinal inflammationProinflammatory stateColitis modelMarrow transplantationNOD2 mutationsRisk factorsT cellsPaneth cells
2008
Combined Th2 cytokine deficiency in donor T cells aggravates experimental acute graft-vs-host disease
Tawara I, Maeda Y, Sun Y, Lowler K, Liu C, Toubai T, McKenzie A, Reddy P. Combined Th2 cytokine deficiency in donor T cells aggravates experimental acute graft-vs-host disease. Experimental Hematology 2008, 36: 988-996. PMID: 18410989, PMCID: PMC2603625, DOI: 10.1016/j.exphem.2008.02.010.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAnimalsBone Marrow TransplantationCD4-Positive T-LymphocytesCell ProliferationDisease Models, AnimalEnzyme-Linked Immunosorbent AssayFemaleFlow CytometryGraft vs Host DiseaseImmunologic TestsInterleukin-2 Receptor alpha SubunitInterleukinsMajor Histocompatibility ComplexMiceMice, Inbred BALB CMice, Inbred C57BLSurvival RateT-LymphocytesTh2 CellsTransplantation, HomologousConceptsDonor T cellsT cellsWT T cellsTh2 cytokinesAcute graftAllogeneic bone marrow transplantationAllogeneic antigen-presenting cellsT cell proliferative responsesAnti-CD3 monoclonal antibodyEnhanced T cell proliferationExperimental acute graftNumber of immunoregulatoryTarget organ damageTh2 cytokine secretionBone marrow transplantationT helper 1Antigen-presenting cellsWild-type T cellsT cell proliferationGreater clinical severityBALB/cB6 recipientsGVHD mortalityHost diseaseIL-17
2005
A crucial role for antigen-presenting cells and alloantigen expression in graft-versus-leukemia responses
Reddy P, Maeda Y, Liu C, Krijanovski O, Korngold R, Ferrara J. A crucial role for antigen-presenting cells and alloantigen expression in graft-versus-leukemia responses. Nature Medicine 2005, 11: 1244-1249. PMID: 16227991, DOI: 10.1038/nm1309.Peer-Reviewed Original ResearchConceptsBone marrow transplantationAllogeneic bone marrow transplantationGVL responseLeukemia responseAlloantigen expressionInduction of graftAntigen-presenting cellsHost diseaseSerious complicationsDonor APCsMarrow transplantationTumor burdenTumor modelGraftAPCHost originPotent formResponseImmunotherapyCellsComplicationsTransplantationAcuityExpressionTumorsCritical 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
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
Acute graft-versus-host disease does not require alloantigen expression on host epithelium
Teshima T, Ordemann R, Reddy P, Gagin S, Liu C, Cooke K, Ferrara J. Acute graft-versus-host disease does not require alloantigen expression on host epithelium. Nature Medicine 2002, 8: 575-581. PMID: 12042807, DOI: 10.1038/nm0602-575.Peer-Reviewed Original ResearchConceptsAntigen-presenting cellsHost antigen-presenting cellsAlloantigen expressionAcute GVHDHost diseaseTarget epitheliaMajor histocompatibility complex class ICD8-mediated GVHDBone marrow chimerasHistocompatibility complex class IClass II alloantigensTumor necrosis factorComplex class IAcute graftInflammatory cytokinesEffector mechanismsGVHDNecrosis factorMouse modelAntigen specificityTissue damageClass IHost epitheliumEpitheliumGraftEnhanced allostimulatory activity of host antigen-presenting cells in old mice intensifies acute graft-versus-host disease
Ordemann R, Hutchinson R, Friedman J, Burakoff S, Reddy P, Duffner U, Braun T, Liu C, Teshima T, Ferrara J. Enhanced allostimulatory activity of host antigen-presenting cells in old mice intensifies acute graft-versus-host disease. Journal Of Clinical Investigation 2002, 109: 1249-1256. PMID: 11994414, PMCID: PMC150964, DOI: 10.1172/jci14793.Peer-Reviewed Original ResearchMeSH KeywordsAgingAnimalsAntigen-Presenting CellsBone Marrow TransplantationCells, CulturedDisease Models, AnimalFemaleGraft vs Host DiseaseHumansIntestine, SmallKiller Cells, NaturalLipopolysaccharidesLymphocyte ActivationMiceMice, Inbred C57BLSurvival RateT-Lymphocyte SubsetsTransplantation ChimeraTransplantation, HomologousTumor Necrosis Factor-alphaConceptsAntigen-presenting cellsDonor T-cell responsesHost antigen-presenting cellsT cell responsesOld miceAcute graftAllogeneic BMTHost diseaseOlder recipientsBM chimerasBMT modelT cellsCell responsesBone marrow transplantation recipientsDonor T cellsMore TNF-alphaMarrow transplantation recipientsMurine BMT modelHitherto unsuspected mechanismAcute GVHDAllostimulatory activityGVHD mortalitySevere GVHDWorse GVHDYoung BM