2014
A Small-Molecule c-Rel Inhibitor Reduces Alloactivation of T Cells without Compromising Antitumor Activity
Shono Y, Tuckett A, Ouk S, Liou H, Altan-Bonnet G, Tsai J, Oyler J, Smith O, West M, Singer N, Doubrovina E, Pankov D, Undhad C, Murphy G, Lezcano C, Liu C, O'Reilly R, van den Brink M, Zakrzewski J. A Small-Molecule c-Rel Inhibitor Reduces Alloactivation of T Cells without Compromising Antitumor Activity. Cancer Discovery 2014, 4: 578-591. PMID: 24550032, PMCID: PMC4011979, DOI: 10.1158/2159-8290.cd-13-0585.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsFemaleGene Expression RegulationGraft vs Host DiseaseGraft vs Tumor EffectHematopoietic Stem Cell TransplantationHumansLymphocyte ActivationMiceMice, Inbred BALB CMice, Inbred C57BLProto-Oncogene Proteins c-relReceptors, Antigen, T-CellSmall Molecule LibrariesT-LymphocytesTransplantation, HomologousConceptsT cellsC-Rel activityAllogeneic hematopoietic stem cell transplantationHematopoietic stem cell transplantationEffector T cellsRegulatory T cellsIL-2 levelsStem cell transplantationAntigen-specific cytotoxicityC-Rel-deficient T cellsC-RelHuman T cellsT cell receptor activationGut homingGVT activityImmunomodulatory therapyInhibitor administrationCell transplantationTumor activityImmune systemReceptor activationPharmaceutical inhibitionSmall molecule-based inhibitionAlloactivationBroad suppression
2013
Pharmacologic inhibition of PKCα and PKCθ prevents GVHD while preserving GVL activity in mice
Haarberg K, Li J, Heinrichs J, Wang D, Liu C, Bronk C, Kaosaard K, Owyang A, Holland S, Masuda E, Tso K, Blazar B, Anasetti C, Beg A, Yu X. Pharmacologic inhibition of PKCα and PKCθ prevents GVHD while preserving GVL activity in mice. Blood 2013, 122: 2500-2511. PMID: 23908466, PMCID: PMC3790515, DOI: 10.1182/blood-2012-12-471938.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell SeparationDisease Models, AnimalEnzyme InhibitorsFlow CytometryGraft vs Host DiseaseGraft vs Leukemia EffectHematopoietic Stem Cell TransplantationIsoenzymesLeukemiaLymphocyte ActivationLymphomaMiceMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutProtein Kinase CProtein Kinase C-alphaProtein Kinase C-thetaT-LymphocytesConceptsHematopoietic cell transplantationDonor T cell proliferationAllogeneic hematopoietic cell transplantationT cell proliferationGVL activityGVL effectCytokine productionT cellsPharmacologic inhibitionChemokine/cytokine productionT-cell cytotoxicDonor T cellsPreclinical murine modelsPotential therapeutic targetT cell activationGVHD inductionGVHD preventionPrevents GVHDHost diseaseLeukemia effectSevere graftTherapeutic optionsCell transplantationEffective therapyPharmacologic approachesPLZF 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 functionsGVHDc‐Rel is an essential transcription factor for the development of acute graft‐versus‐host disease in mice
Yu Y, Wang D, Kaosaard K, Liu C, Fu J, Haarberg K, Anasetti C, Beg A, Yu X. c‐Rel is an essential transcription factor for the development of acute graft‐versus‐host disease in mice. European Journal Of Immunology 2013, 43: 2327-2337. PMID: 23716202, PMCID: PMC3940138, DOI: 10.1002/eji.201243282.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone Marrow TransplantationCell DifferentiationCell ProliferationForkhead Transcription FactorsGraft vs Host DiseaseImmune ToleranceLymphocyte ActivationMiceMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutProto-Oncogene Proteins c-relTh1 CellsTh17 CellsT-Lymphocytes, RegulatoryTransplantation, HomologousConceptsT cellsAcute GVHDHost diseaseAllogeneic bone marrow transplantationAllogeneic hematopoietic cell transplantationC-RelGVHD target organsHematopoietic cell transplantationRegulatory T cellsBone marrow transplantationAcute graftLeukemia responseTransplant toleranceAllogeneic recipientsMarrow transplantationMinor histocompatibilityCell transplantationTh1 cellsLymphoid organsMurine modelTarget organsTherapeutic interventionsNF-κB familyGraftPotential targetPhosphatidylinositol 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 transplantation
2012
LBH589 Enhances T Cell Activation In Vivo and Accelerates Graft-versus-Host Disease in Mice
Wang D, Iclozan C, Liu C, Xia C, Anasetti C, Yu X. LBH589 Enhances T Cell Activation In Vivo and Accelerates Graft-versus-Host Disease in Mice. Transplantation And Cellular Therapy 2012, 18: 1182-1190.e1. PMID: 22698484, PMCID: PMC3417119, DOI: 10.1016/j.bbmt.2012.06.002.Peer-Reviewed Original ResearchConceptsBone marrow transplantSuberoylanilide hydroxamic acidAllogeneic bone marrow transplantAllogeneic transplant modelElevated Th1 cytokinesPrevention of GVHDDonor T cellsT cell infiltrationHistone deacetylase inhibitorsT cell activationTumor cell growthCXCR3 expressionHost diseaseRecipient serumPan-HDACiTh1 cytokinesMarrow transplantProinflammatory cytokinesTransplant modelCell infiltrationInflammatory diseasesGVHDT cellsMouse modelDisease amelioration
2011
Host 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 transplantationRoles of CD28, CTLA4, and Inducible Costimulator in Acute Graft-versus-Host Disease in Mice
Li J, Semple K, Suh W, Liu C, Chen F, Blazar B, Yu X. Roles of CD28, CTLA4, and Inducible Costimulator in Acute Graft-versus-Host Disease in Mice. Transplantation And Cellular Therapy 2011, 17: 962-969. PMID: 21447398, PMCID: PMC3131782, DOI: 10.1016/j.bbmt.2011.01.018.Peer-Reviewed Original ResearchMeSH KeywordsAbataceptAcute DiseaseAnimalsAntigens, CDAntigens, Differentiation, T-LymphocyteB7-1 AntigenB7-2 AntigenBone Marrow TransplantationCD28 AntigensCTLA-4 AntigenFas Ligand ProteinGraft vs Host DiseaseImmune ToleranceImmunoconjugatesInducible T-Cell Co-Stimulator ProteinInterferon-gammaLymphocyte ActivationMiceMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutRadiation ChimeraT-Lymphocyte SubsetsTransplantation, HomologousTumor Necrosis Factor-alphaConceptsAllogeneic bone marrow transplantationBone marrow transplantationInducible costimulatorRole of CD28T cellsCTLA4 signalsHost diseaseMarrow transplantationMyeloablative allogeneic bone marrow transplantationPathogenic T cell responsesDevelopment of GVHDSeverity of GVHDT cell responsesT cell toleranceAbsence of B7T cell activationAcute graftAcute GVHDICOS signalingPrevents GVHDCTLA4-IgCD28 familyGVHDEffector functionsCell toleranceManipulating 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
A Crucial Role for Host APCs in the Induction of Donor CD4+CD25+ Regulatory T Cell-Mediated Suppression of Experimental Graft-versus-Host Disease
Tawara I, Shlomchik WD, Jones A, Zou W, Nieves E, Liu C, Toubai T, Duran-Struuck R, Sun Y, Clouthier SG, Evers R, Lowler KP, Levy RB, Reddy P. A Crucial Role for Host APCs in the Induction of Donor CD4+CD25+ Regulatory T Cell-Mediated Suppression of Experimental Graft-versus-Host Disease. The Journal Of Immunology 2010, 185: 3866-3872. PMID: 20810991, PMCID: PMC2981818, DOI: 10.4049/jimmunol.1001625.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigen PresentationAntigen-Presenting CellsBone Marrow TransplantationCell SeparationDisease Models, AnimalFlow CytometryGraft vs Host DiseaseHistocompatibility Antigens Class IIInterleukin-2 Receptor alpha SubunitLymphocyte ActivationMiceMice, Inbred BALB CMice, Inbred C57BLT-Lymphocyte SubsetsT-Lymphocytes, RegulatoryConceptsSuppression of GVHDDonor T cellsHost APCsBone marrow transplantationDonor TregsT cellsHost diseaseMarrow transplantationRegulatory T cell-mediated suppressionAlloreactive donor T cellsAllogeneic bone marrow transplantationT cell-mediated suppressionInduction of donorInduction of GVHDRegulatory T cellsCell-mediated suppressionDevelopment of graftExperimental GVHDGVHD protectionTreg numbersIL-10Nonmalignant diseasesAlloantigen expressionGVHDMurine modelAbsence 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 diseaseSecondary 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
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 CellsThymus GlandT-LymphocytesTNF-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 reconstitutionNOD2 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 cellsCytolytic T cells induce ceramide-rich platforms in target cell membranes to initiate graft-versus-host disease
Rotolo J, Stancevic B, Lu S, Zhang J, Suh D, King C, Kappel L, Murphy G, Liu C, Fuks Z, van den Brink M, Kolesnick R. Cytolytic T cells induce ceramide-rich platforms in target cell membranes to initiate graft-versus-host disease. Blood 2009, 114: 3693-3706. PMID: 19666872, PMCID: PMC2766684, DOI: 10.1182/blood-2008-11-191148.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBone Marrow TransplantationCD8-Positive T-LymphocytesCell MembraneCeramidesCytokinesDisease Models, AnimalFemaleGraft vs Host DiseaseHepatocytesInterferon-gammaIntestine, SmallLiverLymphocyte ActivationMaleMiceMice, Inbred C57BLMice, Inbred MRL lprMice, SCIDSkinSphingomyelin PhosphodiesteraseSurvival RateT-Lymphocytes, CytotoxicConceptsHost diseaseT cellsT cell proliferation/activationAllogeneic bone marrowAcute inflammatory phaseRelevant mouse modelTumor necrosis factorCytolytic T cellsProliferation/activationCytolytic T lymphocytesPotential new targetsHost target cellsTarget cell membraneAcute graftAcute GVHDGVHD progressionCytokine stormOrgan injuryNecrosis factorGVHDInflammatory phaseRelevant graftT lymphocytesMouse modelBone marrow
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
β2 integrins separate graft-versus-host disease and graft-versus-leukemia effects
Liang Y, Liu C, Djeu J, Zhong B, Peters T, Scharffetter-Kochanek K, Anasetti C, Yu X. β2 integrins separate graft-versus-host disease and graft-versus-leukemia effects. Blood 2007, 111: 954-962. PMID: 17928532, PMCID: PMC2200850, DOI: 10.1182/blood-2007-05-089573.Peer-Reviewed Original ResearchConceptsT cellsHost diseaseLeukemia effectMurine allogeneic bone marrow transplantation modelAllogeneic bone marrow transplantation modelWild-type donor T cellsAllogeneic hematopoietic stem cell transplantationDonor T-cell infiltrationDonor-derived T cellsHematopoietic stem cell transplantationBeta2 integrinsAnalysis of alloreactivityLess GVHD morbidityDevelopment of GVHDDonor T cellsGVHD target organsT cell infiltrationBone marrow transplantation modelStem cell transplantationWT T cellsT cell activationGVHD morbidityGVL activityGVL effectLess GVHDCCR1/CCL5 (RANTES) receptor-ligand interactions modulate allogeneic T-cell responses and graft-versus-host disease following stem-cell transplantation
Choi S, Hildebrandt G, Olkiewicz K, Hanauer D, Chaudhary M, Silva I, Rogers C, Deurloo D, Fisher J, Liu C, Adams D, Chensue S, Cooke K. CCR1/CCL5 (RANTES) receptor-ligand interactions modulate allogeneic T-cell responses and graft-versus-host disease following stem-cell transplantation. Blood 2007, 110: 3447-3455. PMID: 17641205, PMCID: PMC2200916, DOI: 10.1182/blood-2007-05-087403.Peer-Reviewed Original ResearchConceptsStem cell transplantationT cell responsesCCR1 expressionHost diseaseT cellsAllogeneic T-cell responsesAllogeneic stem cell transplantationCCR1-deficient miceDevelopment of GVHDCytolytic effector functionDonor cellsT cell functionChemokine receptor-ligand interactionsT cell proliferationHost target tissuesReceptor-ligand interactionsActivated T cellsAcute graftGVHD mortalityGVL activityIFNgamma secretionAllo-SCTGVHD severityLeukemic infiltrationLeukemic relapse