2023
Ambient oxygen levels regulate intestinal dysbiosis and GVHD severity after allogeneic stem cell transplantation
Seike K, Kiledal A, Fujiwara H, Henig I, Burgos da Silva M, van den Brink M, Hein R, Hoostal M, Liu C, Oravecz-Wilson K, Lauder E, Li L, Sun Y, Schmidt T, Shah Y, Jenq R, Dick G, Reddy P. Ambient oxygen levels regulate intestinal dysbiosis and GVHD severity after allogeneic stem cell transplantation. Immunity 2023, 56: 353-368.e6. PMID: 36736321, DOI: 10.1016/j.immuni.2023.01.007.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDysbiosisGastrointestinal DiseasesGraft vs Host DiseaseHematopoietic Stem Cell TransplantationIntestinesMiceConceptsGraft-versus-host diseaseAmbient oxygen levelsGI graft-versus-host diseaseGut microbiome compositionMicrobiome-dependent mannerMicrobiome compositionMicrobial structureOxygen levelsIntestinal dysbiosisGraft-versus-host disease severityDysbiosisAllogeneic stem cell transplantationAnaerobic commensalsPathogenic T cellsStem cell transplantationIntestinal diseaseInflammatory bowel diseaseGastrointestinal (GI) diseasesCell transplantationIntestinal pathologyT cellsHostBowel diseaseHIF-1aIntestinal damage
2015
Mature T cell responses are controlled by microRNA-142
Sun Y, Oravecz-Wilson K, Mathewson N, Wang Y, McEachin R, Liu C, Toubai T, Wu J, Rossi C, Braun T, Saunders T, Reddy P. Mature T cell responses are controlled by microRNA-142. Journal Of Clinical Investigation 2015, 125: 2825-2840. PMID: 26098216, PMCID: PMC4563679, DOI: 10.1172/jci78753.Peer-Reviewed Original ResearchConceptsCell cyclingE2F transcription factorsAtypical E2F transcription factorMature T cell responsesCell proliferationShort palindromic repeatsUpregulation of genesMiR-142T cell developmentTranscription factorsBioinformatics analysisTarget genesPalindromic repeatsMolecular approachesMolecular mechanismsCell developmentMolecular processesMicroRNA-142Targeted deletionWT T cellsGenesE2F8E2F7Multiple murine modelsT cell proliferationHuman 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
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 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 ResearchMeSH KeywordsAnimalsBacteriaCell DifferentiationCell ProliferationDisease Models, AnimalGraft vs Host DiseaseMiceSeverity of Illness IndexT-LymphocytesConceptsSeverity of GVHDDonor microbiotaHost diseaseT cellsT cell-mediated alloresponsesGerm-free donorsSeverity of graftAlloreactive T cellsRelevant murine modelImmune responseMurine modelRecipient microbiotaExperimental graftGVHDSeverityMicrobiotaRecent dataGraftMicrobial floraAlloresponsesCellsDiseaseInterleukin-22 Protects Intestinal Stem Cells from Immune-Mediated Tissue Damage and Regulates Sensitivity to Graft versus Host Disease
Hanash A, Dudakov J, Hua G, O’Connor M, Young L, Singer N, West M, Jenq R, Holland A, Kappel L, Ghosh A, Tsai J, Rao U, Yim N, Smith O, Velardi E, Hawryluk E, Murphy G, Liu C, Fouser L, Kolesnick R, Blazar B, van den Brink M. Interleukin-22 Protects Intestinal Stem Cells from Immune-Mediated Tissue Damage and Regulates Sensitivity to Graft versus Host Disease. Immunity 2012, 37: 339-350. PMID: 22921121, PMCID: PMC3477611, DOI: 10.1016/j.immuni.2012.05.028.Peer-Reviewed Original ResearchConceptsIL-23-responsive innate lymphoid cellsIntestinal IL-22IL-22Intestinal stem cellsTissue damageHost diseaseTransplant recipientsIL-22 deficiencyInflammatory intestinal damageDonor immune systemInnate lymphoid cellsBone marrow transplantIL-22 receptorStem cellsILC frequenciesPretransplant conditioningIntestinal damageMarrow transplantCrypt apoptosisLymphoid cellsImmune systemGVHDTissue sensitivityProtective factorsEpithelial integrityLBH589 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 ameliorationRegulation of intestinal inflammation by microbiota following allogeneic bone marrow transplantation
Jenq R, Ubeda C, Taur Y, Menezes C, Khanin R, Dudakov J, Liu C, West M, Singer N, Equinda M, Gobourne A, Lipuma L, Young L, Smith O, Ghosh A, Hanash A, Goldberg J, Aoyama K, Blazar B, Pamer E, van den Brink M. Regulation of intestinal inflammation by microbiota following allogeneic bone marrow transplantation. Journal Of Experimental Medicine 2012, 209: 903-911. PMID: 22547653, PMCID: PMC3348096, DOI: 10.1084/jem.20112408.Peer-Reviewed Original ResearchConceptsAllogeneic bone marrow transplantationBone marrow transplantationIntestinal inflammationMarrow transplantationAllogeneic BMT recipientsPotential risk factorsSubsequent GVHDHost diseaseBMT recipientsRisk factorsGVHDMouse modelResident gut microbesInflammationIntestinal microbiotaSignificant protectionGut floraHuman recipientsHuman floraInitial onsetGut microbesLongitudinal studyTransplantationMicrobiotaMiceRepertoire Enhancement with Adoptively Transferred Female Lymphocytes Controls the Growth of Pre-Implanted Murine Prostate Cancer
Jenq R, Curran M, Goldberg G, Liu C, Allison J, van den Brink M. Repertoire Enhancement with Adoptively Transferred Female Lymphocytes Controls the Growth of Pre-Implanted Murine Prostate Cancer. PLOS ONE 2012, 7: e35222. PMID: 22493742, PMCID: PMC3320876, DOI: 10.1371/journal.pone.0035222.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAnimalsAntigens, NeoplasmCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesDEAD-box RNA HelicasesFemaleGraft vs Host DiseaseHumansImmunotherapy, AdoptiveLymphocyte CountMaleMiceMinor Histocompatibility AntigensNeoplasm TransplantationProstatic NeoplasmsSex FactorsWhole-Body IrradiationConceptsCD4 T cellsT cellsProstatic adenocarcinoma cellsAdoptive transferProstate cancerEffective anti-tumor immune responseCancer-reactive T cellsCD8 T cell responsesHigh-affinity T cellsPotential tumor rejection antigensTRAMP-C2 tumor cellsAnti-tumor immune responseAdenocarcinoma cellsExacerbation of graftPresence of CD25Female lymphocytesRegulatory T cellsAdoptive transfer modelReactive T cellsT cell responsesT cell repertoireMurine prostate cancerProstate cancer antigenAdult male hostsTumor rejection antigensDonor- but not host-derived interleukin-10 contributes to the regulation of experimental graft-versus-host disease
Tawara I, Sun Y, Liu C, Toubai T, Nieves E, Evers R, Alrubaie M, Mathewson N, Tamaki H, Reddy P. Donor- but not host-derived interleukin-10 contributes to the regulation of experimental graft-versus-host disease. Journal Of Leukocyte Biology 2012, 91: 667-675. PMID: 22262800, PMCID: PMC3317273, DOI: 10.1189/jlb.1011510.Peer-Reviewed Original ResearchConceptsSuppression of GVHDSeverity of GVHDIL-10Donor TregsBM graftsRegulation of GVHDImmune-regulatory cytokinesInterleukin-10 contributeAcute GVHDClinical GVHDGVHD severityHost diseaseDonor graftsGVHDPreclinical modelsTregsGene polymorphismsExperimental graftCellular subsetsGraftSeverityHost cellsFunctional relevanceHost tissuesIL
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 dataDiseasePrevention of GVHD while sparing GVL effect by targeting Th1 and Th17 transcription factor T-bet and RORγt in mice
Yu Y, Wang D, Liu C, Kaosaard K, Semple K, Anasetti C, Yu X. Prevention of GVHD while sparing GVL effect by targeting Th1 and Th17 transcription factor T-bet and RORγt in mice. Blood 2011, 118: 5011-5020. PMID: 21856864, PMCID: PMC3208306, DOI: 10.1182/blood-2011-03-340315.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsCells, CulturedCombined Modality TherapyGraft vs Host DiseaseGraft vs Leukemia EffectHematopoietic Stem Cell TransplantationLeukemiaMiceMice, Inbred C57BLMice, KnockoutMolecular Targeted TherapyNuclear Receptor Subfamily 1, Group F, Member 3T-Box Domain ProteinsTh1 CellsTh17 CellsTransplantation, HomologousConceptsHematopoietic cell transplantationGVL effectT-betT cellsTranscription factor T-betPrevention of GVHDDonor T cellsCD8 T cellsAmeliorated GVHDGVL activityNaive ThTh17 subsetAdoptive transferCell transplantationTh17 differentiationEffective therapyHematologic malignanciesAllogeneic hostsGVHDMajor MHCTh1Regulatory phenotypeSkewed differentiationTargeted disruptionRORγtCeacam1 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 transplantationAbrogation of donor T-cell IL-21 signaling leads to tissue-specific modulation of immunity and separation of GVHD from GVL
Hanash A, Kappel L, Yim N, Nejat R, Goldberg G, Smith O, Rao U, Dykstra L, Na I, Holland A, Dudakov J, Liu C, Murphy G, Leonard W, Heller G, van den Brink M. Abrogation of donor T-cell IL-21 signaling leads to tissue-specific modulation of immunity and separation of GVHD from GVL. Blood 2011, 118: 446-455. PMID: 21596854, PMCID: PMC3138694, DOI: 10.1182/blood-2010-07-294785.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsGene Knockdown TechniquesGraft vs Host DiseaseGraft vs Leukemia EffectHumansImmunity, InnateInterleukin-21 Receptor alpha SubunitInterleukinsLymphocytes, Tumor-InfiltratingMiceMice, Inbred BALB CMice, Inbred C57BLMice, Inbred DBAMice, KnockoutOrgan SpecificitySignal TransductionTissue DonorsT-LymphocytesTransplantation ImmunologyConceptsSeparation of GVHDDonor T cellsKO T cellsIL-21T cellsTissue-specific modulationGastrointestinal GVHDCytokine productionWild-type donor T cellsDonor regulatory T cellsTh cell cytokine productionPeripheral T cell functionMesenteric lymph nodesRegulatory T cellsTh cell functionIL-21 signalingInflammatory cytokine productionBM transplantation modelT cell functionLymphoma responseLymph nodesProinflammatory cytokinesTransplantation outcomesTransplantation modelGVHD