2015
Human Mesenchymal Stromal Cells Attenuate Graft‐Versus‐Host Disease and Maintain Graft‐Versus‐Leukemia Activity Following Experimental Allogeneic Bone Marrow Transplantation
Auletta J, Eid S, Wuttisarnwattana P, Silva I, Metheny L, Keller M, Guardia‐Wolff R, Liu C, Wang F, Bowen T, Lee Z, Solchaga L, Ganguly S, Tyler M, Wilson D, Cooke K. Human Mesenchymal Stromal Cells Attenuate Graft‐Versus‐Host Disease and Maintain Graft‐Versus‐Leukemia Activity Following Experimental Allogeneic Bone Marrow Transplantation. Stem Cells 2015, 33: 601-614. PMID: 25336340, PMCID: PMC4304927, DOI: 10.1002/stem.1867.Peer-Reviewed Original ResearchConceptsT cell expansionT cell proliferationGraft-VersusHost diseaseLeukemia activityExperimental allogeneic bone marrow transplantationDonor T cell expansionAllogeneic bone marrow transplantationCytotoxic T cell activityAlloreactive T cell proliferationPotent GVL effectCyclo-oxygenase inhibitionT cell activityT cell suppressionBone marrow transplantationMarrow-derived mesenchymal stromal cellsSecondary lymphoid organsSplenic T cellsSplenic marginal zoneMixed leukocyte cultureMesenchymal stromal cellsBMT miceEP2 agonismGVL activityGVL effect
2012
CD24-Siglec-G Interaction Plays an Important in Reducing Experimental Graft-Versus-Host Disease (GVHD)
Toubai T, Evers R, Sun Y, Tawara I, Liu C, Tamaki H, Mathewson N, Nieves E, Bassetti M, Zheng P, Liu Y, Reddy P. CD24-Siglec-G Interaction Plays an Important in Reducing Experimental Graft-Versus-Host Disease (GVHD). Blood 2012, 120: 453. DOI: 10.1182/blood.v120.21.453.453.Peer-Reviewed Original ResearchHost antigen presenting cellsAntigen presenting cellsBALB/c donorsT cellsWT B6Allogeneic BMTImmunoreceptor tyrosine-based inhibitory motifWorse survivalSerum levelsImmune activationBM chimerasDonor T cell expansionAllogeneic T-cell responsesT cell responsesBALB/c T cellsPro-inflammatory cytokinesT cell expansionRelevant murine modelRole of SiglecsC donorsIg-like lectinsIntensity of conditioningGraft-VersusGVHD mortalityHigher GVHD
2011
Pretransplant 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 macrophagesIkaros-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
Ikaros Deficiency Enhances Notch Signaling in Host Antigen Presenting Cells and Differentially Regulates Gvhd and GVL Responses After Experimental BMT.
Toubai T, Sun Y, Tawara I, Malter C, Lowler K, Nieves E, Liu C, Maillard I, Winandy S, Reddy P. Ikaros Deficiency Enhances Notch Signaling in Host Antigen Presenting Cells and Differentially Regulates Gvhd and GVL Responses After Experimental BMT. Blood 2009, 114: 690. DOI: 10.1182/blood.v114.22.690.690.Peer-Reviewed Original ResearchDendritic cellsHost APCsGVL responseT cellsDonor T cell expansionHost antigen presenting cellsAllo-stimulatory capacityB6 dendritic cellsCertain dendritic cellsModel of GVHDNumber of PDCsInduction of graftAllogeneic T cellsT cell expansionAntigen presenting cellsComprehensive cancer centerBlockade of NotchStrain-independent mannerΓ-secretase inhibitorPutative molecular targetsMichigan Comprehensive Cancer CenterRate of apoptosisAcute GVHDGvH responseGVHD response
2006
Secondary Lymphoid Tissues Are Not Required for the Induction of GVHD Following Allogeneic BMT: A Shifting Paradigm for T Cell Allo-Activation.
Silva I, Olkiewicz K, Fisher J, Chaudhary M, Vannella K, Deurloo D, Choi S, Liu C, Cooke K. Secondary Lymphoid Tissues Are Not Required for the Induction of GVHD Following Allogeneic BMT: A Shifting Paradigm for T Cell Allo-Activation. Blood 2006, 108: 3170. DOI: 10.1182/blood.v108.11.3170.3170.Peer-Reviewed Original ResearchBone marrow transplantationAllo-BMT recipientsAntigen presenting cellsHost antigen presenting cellsAllogeneic bone marrow transplantationAly/aly miceInduction of GVHDSecondary lymphoid tissuesPeyer's patchesAllo-BMTAly miceLymphoid tissueT cellsLittermate controlsDonor T cell activationDonor T cell expansionWild-type B6 recipientsAllo-stimulatory capacitySyngeneic BMT recipientsDonor T cellsOnly curative optionSeverity of GVHDBALB/c T cellsIFN-γ productionT cell expansion
2005
Critical Role for CCR1:CCL5 (RANTES) Receptor Ligand Interactions in Modulating Allogeneic T Cell Responses Following Bone Marrow Transplantation.
Choi S, Hildebrandt G, Silva I, Olkiewicz K, Chensue S, Liu C, Chaudhary M, Fisher J, Lane T, Cooke K. Critical Role for CCR1:CCL5 (RANTES) Receptor Ligand Interactions in Modulating Allogeneic T Cell Responses Following Bone Marrow Transplantation. Blood 2005, 106: 3107. DOI: 10.1182/blood.v106.11.3107.3107.Peer-Reviewed Original ResearchT cell responsesGVL effectAllo-SCTT cellsCell responsesChemokine receptorsAllogeneic T-cell responsesAllo-SCT recipientsDonor T-cell alloreactivityGVHD target tissuesSerum IFNγ levelsSeverity of GVHDTarget tissuesLeukemia-free survivalClinical scoring systemBone marrow transplantationT cell expansionT-cell alloreactivityBone marrow inoculumHost target tissuesActivated T cellsP815 tumor cellsDose-dependent mannerHigher tumor dosesAcute graftCritical 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 γd T cells Exacerbate Experimental Acute Graft-Versus-Host Disease through Activation of Host Antigen Presenting Cells.
Maeda Y, Reddy P, Liu C, Bishop D, Ferrara J. Host γd T cells Exacerbate Experimental Acute Graft-Versus-Host Disease through Activation of Host Antigen Presenting Cells. Blood 2004, 104: 3045. DOI: 10.1182/blood.v104.11.3045.3045.Peer-Reviewed Original ResearchHost dendritic cellsDendritic cellsT cellsB6 hostsDonor T cell expansionHost antigen presenting cellsBALB/c donorsAcute Graft-VersusB6 dendritic cellsControl dendritic cellsFull-intensity conditioningWT dendritic cellsSeverity of GVHDDonor T cellsAllogeneic T cellsT cell expansionWild-type B6Spleen T cellsAntigen presenting cellsSplenic T cellsMHC class IICells 24 hrNew therapeutic targetsDisease target tissuesT cell receptorCCR1 Expression on Donor Leukocytes Is Critical to the Development of Graft Versus Host Disease after Allogeneic SCT.
Hildebrandt G, Choi S, Olkiewicz K, Chensue S, Liu C, Cooke K. CCR1 Expression on Donor Leukocytes Is Critical to the Development of Graft Versus Host Disease after Allogeneic SCT. Blood 2004, 104: 3067. DOI: 10.1182/blood.v104.11.3067.3067.Peer-Reviewed Original ResearchT cell responsesAllo-SCTCCR1 expressionDonor leukocytesHost diseaseT cellsCell responsesDonor T-cell responsesGraft Versus Host DiseaseAllogeneic stem cell transplantationSerum IFNγ levelsTranslocation of endotoxinVersus Host DiseaseDonor T cellsSeverity of GVHDDonor cellsClinical scoring systemStem cell transplantationT cell expansionAcute graftGVL effectSignificant GVHDTNFa levelsAllogeneic SCTClinical GVHDIncreasing T-cell age reduces effector activity but preserves proliferative capacity in a murine allogeneic major histocompatibility complex-mismatched bone marrow transplant model
Friedman J, Alpdogan O, van den Brink M, Liu C, Hurwitz D, Boyd A, Kupper T, Burakoff S. Increasing T-cell age reduces effector activity but preserves proliferative capacity in a murine allogeneic major histocompatibility complex-mismatched bone marrow transplant model. Transplantation And Cellular Therapy 2004, 10: 448-460. PMID: 15205666, DOI: 10.1016/j.bbmt.2004.03.005.Peer-Reviewed Original ResearchConceptsOld T cellsT cellsSurface antigen expressionCD8 cellsAntigen expressionEffector activityT cell receptor repertoireBone marrow transplant modelCD4 T cell expansionT-cell doseSeverity of GVHDType 1 cytokinesT cell expansionAntigen-driven proliferationT-cell groupAdult T-cellT-cell ageSuccinimidyl ester labelingYoung T cellsAge-dependent declineLethal GVHDHost diseasePathologic evidenceTransplant modelCytolytic function
2003
Role of CXCR3-induced donor T-cell migration in acute GVHD
Duffner U, Lu B, Hildebrandt G, Teshima T, Williams D, Reddy P, Ordemann R, Clouthier S, Lowler K, Liu C, Gerard C, Cooke K, Ferrara J. Role of CXCR3-induced donor T-cell migration in acute GVHD. Experimental Hematology 2003, 31: 897-902. PMID: 14550805, DOI: 10.1016/s0301-472x(03)00198-x.Peer-Reviewed Original ResearchConceptsRole of CXCR3T cellsAcute GVHDDonor T cell expansionDonor T cell migrationDonor T cellsExpression of CXCR3GVHD target organsDonor cellsEffector T cellsBone marrow transplantation modelDonor T-cell functionMinor histocompatibility antigensT cell expansionWild-type B6Chemokine receptor CXCR3T cell functionWild-type T cellsWild-type donor cellsT cell migrationMigration of donorWild-type donorsAcute graftHost diseaseBMT recipients
2001
Interleukin-18 Regulates Acute Graft-Versus-Host Disease by Enhancing Fas-mediated Donor T Cell Apoptosis
Reddy P, Teshima T, Kukuruga M, Ordemann R, Liu C, Lowler K, Ferrara J. Interleukin-18 Regulates Acute Graft-Versus-Host Disease by Enhancing Fas-mediated Donor T Cell Apoptosis. Journal Of Experimental Medicine 2001, 194: 1433-1440. PMID: 11714750, PMCID: PMC2193680, DOI: 10.1084/jem.194.10.1433.Peer-Reviewed Original ResearchConceptsDonor T cellsIL-18Acute GVHDHost diseaseT cellsDonor T cell expansionSerum tumor necrosis factorT helper type 1Acute Graft-VersusGamma knockout miceGVHD-related mortalityMurine bone marrow transplantation modelBone marrow transplantation modelHelper type 1T cell expansionTumor necrosis factorFas-deficient miceT cell apoptosisAcute graftGraft-VersusBMT recipientsIntestinal histopathologyTh2 responsesInterleukin-18Transplantation model