2019
T cell–derived interferon-γ programs stem cell death in immune-mediated intestinal damage
Takashima S, Martin M, Jansen S, Fu Y, Bos J, Chandra D, O'Connor M, Mertelsmann A, Vinci P, Kuttiyara J, Devlin S, Middendorp S, Calafiore M, Egorova A, Kleppe M, Lo Y, Shroyer N, Cheng E, Levine R, Liu C, Kolesnick R, Lindemans C, Hanash A. T cell–derived interferon-γ programs stem cell death in immune-mediated intestinal damage. Science Immunology 2019, 4 PMID: 31811055, PMCID: PMC7239329, DOI: 10.1126/sciimmunol.aay8556.Peer-Reviewed Original ResearchConceptsBone marrow transplantationIntestinal stem cellsDonor T cellsStem cell compartmentT cellsStem cell deathEpithelial culturesAllogeneic bone marrow transplantationDysregulated T cell activationT cell-mediated pathologyInhibition of JAK signalingStem cellsImmune-mediated damageActivated T cellsT cell activationCell compartmentCell deathTissue stem cellsPaneth cell nicheIFNg productionMarrow transplantationIntestinal immunopathologyInterferon-gHealthy miceStem cell colonies
2014
T-Bet Is Critical for the Development of Acute Graft-Versus-Host Disease By Regulating Hematopoietic Antigen Presenting Cells
Fu J, Wu Y, Nguyen H, Heinrichs J, Schutt S, Liu C, Anasetti C, Yu X. T-Bet Is Critical for the Development of Acute Graft-Versus-Host Disease By Regulating Hematopoietic Antigen Presenting Cells. Blood 2014, 124: 846. DOI: 10.1182/blood.v124.21.846.846.Peer-Reviewed Original ResearchAntigen presenting cellsDonor T cellsT cell apoptosisAcute GVHDRecipient dendritic cellsDendritic cellsIFN-γ productionT-betT cellsWT T cellsT cell activationHost diseasePresenting cellsAllogeneic hematopoietic stem cell transplantationAPC functionAlloreactive donor T cellsDevelopment of aGVHDDonor T cell activationDonor T-cell responsesAllogeneic bone marrow transplantationHematopoietic stem cell transplantationTranscription factor T-betAcute Graft-VersusInduction of GVHDSevere acute GVHD
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 approachesPhosphatidylinositol 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
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 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 tolerance
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
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 activationβ2 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 GVHD