2015
Targeting Host Complement C3a/C5a Receptors to Control of Acute Graft-Versus-Host Disease in Mice
Nguyen H, Heinrichs J, Fu J, Wu Y, Bastian D, Schutt S, Daenthanasanmak A, Dany M, Liu C, Fairlie D, Tomlinson S, Yu X. Targeting Host Complement C3a/C5a Receptors to Control of Acute Graft-Versus-Host Disease in Mice. Blood 2015, 126: 3076. DOI: 10.1182/blood.v126.23.3076.3076.Peer-Reviewed Original ResearchC3aR/C5aRAntigen presenting cellsDonor T cellsT cellsGVL activityHost diseaseC5aR signalingAlloreactive donor T cellsDonor T cell activationDonor T-cell responsesHost antigen presenting cellsAllogeneic hematopoietic cell transplantationComplement systemAcute Graft-VersusControl of GVHDHost hematopoietic cellsDevelopment of GVHDGVHD target organsAdaptive immune cellsHematopoietic cell transplantationEffector T cellsT cell responsesTotal body irradiationAlloreactive T cellsPro-inflammatory cytokines
2013
PLZF Confers Effector Functions to Donor T Cells That Preserve Graft-versus-Tumor Effects while Attenuating GVHD
Ghosh A, Holland A, Dogan Y, Yim N, Rao U, Young L, West M, Singer N, Lee H, Na I, Tsai J, Jenq R, Penack O, Hanash A, Lezcano C, Murphy G, Liu C, Sadelain M, Sauer M, Sant'Angelo D, van den Brink M. PLZF Confers Effector Functions to Donor T Cells That Preserve Graft-versus-Tumor Effects while Attenuating GVHD. Cancer Research 2013, 73: 4687-4696. PMID: 23733752, PMCID: PMC3732814, DOI: 10.1158/0008-5472.can-12-4699.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsBone Marrow TransplantationFlow CytometryGraft vs Host DiseaseGraft vs Tumor EffectKruppel-Like Transcription FactorsLymphocyte ActivationLymphocyte Culture Test, MixedMiceMice, Inbred BALB CMice, Inbred C57BLNeoplasms, ExperimentalPromyelocytic Leukemia Zinc Finger ProteinT-LymphocytesTransplantation, HomologousConceptsDonor T cellsT cellsPromyelocytic leukemia zinc fingerGVT effectInvariant natural killer T (iNKT) cellsAlloreactive donor T cellsAllogeneic bone marrow transplantationNatural killer T cellsTranscription factor promyelocytic leukemia zinc fingerKiller T cellsAlloreactive T cellsBone marrow transplantationConventional T cellsOverall improved outcomesLess GVHDLower GVHDPreserves graftTumor effectImproved survivalMarrow transplantationCytokine responsesImproved outcomesTumor relapseEffector functionsGVHDPhosphatidylinositol 3-Kinase–Independent Signaling Pathways Contribute to ICOS-Mediated T Cell Costimulation in Acute Graft-Versus-Host Disease in Mice
Li J, Heinrichs J, Leconte J, Haarberg K, Semple K, Liu C, Gigoux M, Kornete M, Piccirillo C, Suh W, Yu X. Phosphatidylinositol 3-Kinase–Independent Signaling Pathways Contribute to ICOS-Mediated T Cell Costimulation in Acute Graft-Versus-Host Disease in Mice. The Journal Of Immunology 2013, 191: 200-207. PMID: 23729441, PMCID: PMC4318500, DOI: 10.4049/jimmunol.1203485.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAnimalsDisease Models, AnimalGene Knock-In TechniquesGraft vs Host DiseaseInducible T-Cell Co-Stimulator ProteinLymphocyte ActivationMiceMice, 129 StrainMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutMice, TransgenicPhosphatidylinositol 3-KinaseSignal TransductionT-Lymphocyte SubsetsConceptsCD8 T cellsCD4 T cellsT cellsHost diseaseWild-type CD8 T cellsCD8 T cell compartmentAllogeneic bone marrow transplantationAcute Graft-VersusPathogenic potentialTotal T cellsAlloreactive T cellsBone marrow transplantationT cell compartmentWild-type T cellsIntracellular calcium mobilizationVivo pathogenic potentialT cell costimulationT cell activationKnockout T cellsAcute graftAcute GVHDGraft-VersusSevere GVHDGVHD modelMarrow transplantationAdoptively transferred TRAIL+ T cells suppress GVHD and augment antitumor activity
Ghosh A, Dogan Y, Moroz M, Holland A, Yim N, Rao U, Young L, Tannenbaum D, Masih D, Velardi E, Tsai J, Jenq R, Penack O, Hanash A, Smith O, Piersanti K, Lezcano C, Murphy G, Liu C, Palomba M, Sauer M, Sadelain M, Ponomarev V, van den Brink M. Adoptively transferred TRAIL+ T cells suppress GVHD and augment antitumor activity. Journal Of Clinical Investigation 2013, 123: 2654-2662. PMID: 23676461, PMCID: PMC3668849, DOI: 10.1172/jci66301.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsAntigen-Presenting CellsCell Line, TumorCytotoxicity, ImmunologicGraft RejectionGraft vs Host DiseaseHEK293 CellsHumansImmunotherapy, AdoptiveLeukemia, Lymphocytic, Chronic, B-CellMiceMice, Inbred BALB CMice, Inbred C57BLNeoplasm TransplantationT-LymphocytesTNF-Related Apoptosis-Inducing LigandConceptsGVT responseT cellsAllo-HSCTAllogeneic hematopoietic stem cell transplantationHematopoietic stem cell transplantationCellular therapyAbsence of GVHDDR5-dependent mannerDonor T cellsAlloreactive T cellsStem cell transplantationChronic lymphocytic leukemia cellsPrecursor T cellsThird-party donorsLymphocytic leukemia cellsApoptosis-inducing ligandGVT activityHost diseaseCell transplantationCurative potentialTumor responseGVHDCertain malignanciesMouse modelHuman leukemia cell lines
2012
Influence of Donor Microbiota on the Severity of Experimental Graft-versus-Host-Disease
Tawara I, Liu C, Tamaki H, Toubai T, Sun Y, Evers R, Nieves E, Mathewson N, Nunez G, Reddy P. Influence of Donor Microbiota on the Severity of Experimental Graft-versus-Host-Disease. Transplantation And Cellular Therapy 2012, 19: 164-168. PMID: 22982686, PMCID: PMC3529780, DOI: 10.1016/j.bbmt.2012.09.001.Peer-Reviewed Original ResearchConceptsSeverity of GVHDDonor microbiotaHost diseaseT cellsT cell-mediated alloresponsesGerm-free donorsSeverity of graftAlloreactive T cellsRelevant murine modelImmune responseMurine modelRecipient microbiotaExperimental graftGVHDSeverityMicrobiotaRecent dataGraftMicrobial floraAlloresponsesCellsDisease
2011
Ceacam1 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 transplantationPretransplant 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 macrophagesManipulating the Bioenergetics of Alloreactive T Cells Causes Their Selective Apoptosis and Arrests Graft-Versus-Host Disease
Gatza E, Wahl D, Opipari A, Sundberg T, Reddy P, Liu C, Glick G, Ferrara J. Manipulating the Bioenergetics of Alloreactive T Cells Causes Their Selective Apoptosis and Arrests Graft-Versus-Host Disease. Science Translational Medicine 2011, 3: 67ra8. PMID: 21270339, PMCID: PMC3364290, DOI: 10.1126/scitranslmed.3001975.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBenzodiazepinesBone Marrow CellsBone Marrow TransplantationFemaleGraft vs Host DiseaseIsoantigensLactatesLymphocyte ActivationMetabolomeMiceMice, Inbred BALB CMice, Inbred C57BLMitochondrial Proton-Translocating ATPasesOxidative PhosphorylationOxygen ConsumptionReactive Oxygen SpeciesT-LymphocytesConceptsAlloreactive T cellsT cellsHost diseaseBM transplantationAerobic glycolysisAdenosine triphosphateAccumulation of acylcarnitinesBone marrow cellsFatty acid oxidationGraft-VersusLymphocyte reconstitutionImmune activationBMT modelBM cellsImmune disordersHematopoietic engraftmentTherapeutic strategiesOxidative phosphorylationSmall molecule inhibitorsMarrow cellsSuperoxide productionSufficient adenosine triphosphateMitochondrial membrane potentialMetabolic adaptationAcid oxidation
2010
Absence of P-Selectin in Recipients of Allogeneic Bone Marrow Transplantation Ameliorates Experimental Graft-versus-Host Disease
Lu S, Holland A, Na I, Terwey T, Alpdogan O, Bautista J, Smith O, Suh D, King C, Kochman A, Hubbard V, Rao U, Yim N, Liu C, Laga A, Murphy G, Jenq R, Zakrzewski J, Penack O, Dykstra L, Bampoe K, Perez L, Furie B, Furie B, van den Brink M. Absence of P-Selectin in Recipients of Allogeneic Bone Marrow Transplantation Ameliorates Experimental Graft-versus-Host Disease. The Journal Of Immunology 2010, 185: 1912-1919. PMID: 20622117, PMCID: PMC3752704, DOI: 10.4049/jimmunol.0903148.Peer-Reviewed Original ResearchConceptsSecondary lymphoid organsDonor T cellsAllogeneic bone marrow transplantationAlloreactive T cellsBone marrow transplantationT cellsWT T cellsP-selectinP-selectin glycoprotein ligand-1P-selectin ligandsMarrow transplantationSmall bowelInflamed tissuesDonor alloreactive T cellsHost disease (GVHD) pathophysiologyGVHD target organsAlloactivated T cellsLigand 1Wild-type recipientsGVHD mortalityGVHD prophylaxisHost diseaseLymphoid organsPeyer's patchesExperimental disease
2009
The cytolytic molecules Fas ligand and TRAIL are required for murine thymic graft-versus-host disease
Na I, Lu S, Yim N, Goldberg G, Tsai J, Rao U, Smith O, King C, Suh D, Hirschhorn-Cymerman D, Palomba L, Penack O, Holland A, Jenq R, Ghosh A, Tran H, Merghoub T, Liu C, Sempowski G, Ventevogel M, Beauchemin N, van den Brink M. The cytolytic molecules Fas ligand and TRAIL are required for murine thymic graft-versus-host disease. Journal Of Clinical Investigation 2009, 120: 343-356. PMID: 19955659, PMCID: PMC2798682, DOI: 10.1172/jci39395.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone Marrow TransplantationCASP8 and FADD-Like Apoptosis Regulating ProteinCell MovementFas Ligand ProteinGraft vs Host DiseaseLymphocyte ActivationMiceMice, Inbred BALB CMice, Inbred C57BLReceptors, OX40Receptors, TNF-Related Apoptosis-Inducing LigandStromal CellsT-LymphocytesThymus GlandTNF-Related Apoptosis-Inducing LigandTransplantation, HomologousConceptsAlloreactive T cellsDonor alloreactive T cellsThymic stromal cellsHost diseaseT cellsDeath receptor 5Thymic graftsProfound T-cell deficiencySelectin glycoprotein ligand-1Stromal cellsPeripheral T cell functionCell adhesion molecule-1Allo-BMT recipientsAllogeneic BM transplantationT-cell reconstitutionT cell deficiencyT cell functionDeath receptor FasAdhesion molecule-1Fas/FasLApoptosis-inducing ligandBMT conditioningSystemic graftP-selectin glycoprotein ligand-1Cell reconstitutionTRAIL/ DR5 Interactions Are Important for Thymic Damage After Allogeneic Bone Marrow Transplantation.
Na I, Lu S, Yim N, Goldberg G, Tsai J, Rao U, Smith O, King C, Suh D, Hirschhorn-Cymerman D, Palomba M, Penack O, Holland A, Jenq R, Ghosh A, Tran H, Merghoub T, Liu C, Sempowski G, Ventevogel M, Beauchemin N, Furie B, van den Brink M. TRAIL/ DR5 Interactions Are Important for Thymic Damage After Allogeneic Bone Marrow Transplantation. Blood 2009, 114: 234. DOI: 10.1182/blood.v114.22.234.234.Peer-Reviewed Original ResearchAlloreactive T cellsDonor alloreactive T cellsAllogeneic bone marrow transplantationT-cell dosePost-transplant periodBone marrow transplantationAllo-BMTT cellsThymic damageThymic cellularityMarrow transplantationCell doseThymic stromaDay 28Early post-transplant periodAllo-BMT recipientsPeri-transplant periodDonor T cellsFas/Fas ligandOvert clinical diseaseSignificant weight lossExpression of DR5TRAIL/DR5 pathwayRole of TRAILAnti-apoptotic protein cFLIP
2008
Organ-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
CEACAM-1 Is Involved in Graft-Versus-Host-Disease in Murine Allogeneic Bone Marrow Transplantation Models.
Lu S, Willis L, Smith M, Suh D, King C, Bautista J, Chow M, Cabrera-Perez J, Hubbard V, Rotolo J, Liu C, Murphy G, Alpdogan O, Blumberg R, Holmes K, Turbide C, Beauchemin N, van den Brink M. CEACAM-1 Is Involved in Graft-Versus-Host-Disease in Murine Allogeneic Bone Marrow Transplantation Models. Blood 2007, 110: 67. DOI: 10.1182/blood.v110.11.67.67.Peer-Reviewed Original ResearchWT T cellsT cellsWT recipientsAdoptive transferSmall bowelMurine allogeneic bone marrow transplantation modelWT controlsAllogeneic bone marrow transplantation modelCarcinoembryonic antigenSplenic regulatory T cellsAllogeneic bone marrow transplantationCEACAM-1Cell adhesion molecule-1Conditioning-related toxicityDonor T cellsGVHD target organsPeripheral lymph nodesRegulatory T cellsAlloreactive T cellsBone marrow transplantation modelBone marrow transplantationDonor bone marrowAdhesion molecule-1T cell apoptosisT cell activation
2005
Absence of β7 integrin results in less graft-versus-host disease because of decreased homing of alloreactive T cells to intestine
Waldman E, Lu S, Hubbard V, Kochman A, Eng J, Terwey T, Muriglan S, Kim T, Heller G, Murphy G, Liu C, Alpdogan O, van den Brink M. Absence of β7 integrin results in less graft-versus-host disease because of decreased homing of alloreactive T cells to intestine. Blood 2005, 107: 1703-1711. PMID: 16291587, PMCID: PMC1895413, DOI: 10.1182/blood-2005-08-3445.Peer-Reviewed Original ResearchConceptsHematopoietic stem cell transplantationLess GVHD morbidityT cell infiltrationT cellsGVHD morbidityGVT activityHost diseaseDonor T-cell infiltrationDonor T cellsAlloreactive T cellsStem cell transplantationWild-type T cellsOverall significant decreaseIntestinal graftIntestinal GVHDLess graftBeta7 integrinCell transplantationCytokine productionAlpha4beta7 integrinIntact activationTumor experimentsMorbidityClinical potentialGraftAbsence of inducible costimulator on alloreactive T cells reduces graft versus host disease and induces Th2 deviation
Hubbard V, Eng J, Ramirez-Montagut T, Tjoe K, Muriglan S, Kochman A, Terwey T, Willis L, Schiro R, Heller G, Murphy G, Liu C, Alpdogan O, van den Brink M. Absence of inducible costimulator on alloreactive T cells reduces graft versus host disease and induces Th2 deviation. Blood 2005, 106: 3285-3292. PMID: 15956289, PMCID: PMC1895338, DOI: 10.1182/blood-2005-01-0410.Peer-Reviewed Original ResearchConceptsAlloreactive T cellsInducible costimulatorT cellsHost diseaseInterleukin-4Allogeneic hematopoietic stem cell transplantationRole of ICOSHematopoietic stem cell transplantationLess GVHD morbidityTh2 immune deviationIL-10 levelsTh1/Th2 developmentMemory T cellsStem cell transplantationWild-type T cellsActivated T cellsCutaneous GVHDGVHD morbidityGVL activityHepatic GVHDImmune deviationLess GVHDTh2 deviationGVHD modelT helper
2003
LPAM (α4β7 integrin) is an important homing integrin on alloreactive T cells in the development of intestinal graft-versus-host disease
Petrovic A, Alpdogan O, Willis L, Eng J, Greenberg A, Kappel B, Liu C, Murphy G, Heller G, van den Brink M. LPAM (α4β7 integrin) is an important homing integrin on alloreactive T cells in the development of intestinal graft-versus-host disease. Blood 2003, 103: 1542-1547. PMID: 14563643, DOI: 10.1182/blood-2003-03-0957.Peer-Reviewed Original ResearchConceptsDonor T cellsT cellsMurine allogeneic bone marrow transplantation modelAllogeneic bone marrow transplantation modelAlloreactive donor T cellsGut-associated lymphoid tissueAdhesion moleculesMucosal addressin cell adhesion moleculeGVHD target organsMesenteric lymph nodesAlloreactive T cellsBone marrow transplantation modelMucosal lymphoid organsHigh endothelial venulesGVHD morbidityGVT activityIntestinal graftIntestinal GVHDLess graftLess GVHDHost diseaseLymph nodesDisease morbidityLymphoid organsLymphoid tissue