2023
Graft-versus-host disease is locally maintained in target tissues by resident progenitor-like T cells
Sacirbegovic F, Günther M, Greco A, Zhao D, Wang X, Zhou M, Rosenberger S, Oberbarnscheidt M, Held W, McNiff J, Jain D, Höfer T, Shlomchik W. Graft-versus-host disease is locally maintained in target tissues by resident progenitor-like T cells. Immunity 2023, 56: 369-385.e6. PMID: 36720219, PMCID: PMC10182785, DOI: 10.1016/j.immuni.2023.01.003.Peer-Reviewed Original ResearchConceptsHost diseaseAllogeneic hematopoietic stem cell transplantationHematopoietic stem cell transplantationChronic antigen stimulationStem cell transplantationAlloreactive effectorsAdoptive transferCell transplantationΑβ TAntigen stimulationCell exhaustionGVHDRecipient tissuesEffector poolMajor causeCell clonesTarget tissuesAffected tissuesDiseaseGraftTissueTCF-1CellsDiseased tissuesMorbidity
2022
TCF7L2 transcriptionally regulates Fgf15 to maintain bile acid and lipid homeostasis through gut‐liver crosstalk
Bhat N, Esteghamat F, Chaube BK, Gunawardhana K, Mani M, Thames C, Jain D, Ginsberg HN, Fernandes‐Hernando C, Mani A. TCF7L2 transcriptionally regulates Fgf15 to maintain bile acid and lipid homeostasis through gut‐liver crosstalk. The FASEB Journal 2022, 36: e22185. PMID: 35133032, PMCID: PMC9624374, DOI: 10.1096/fj.202101607r.Peer-Reviewed Original ResearchConceptsGut-liver crosstalkBile synthesisDiet-induced fatty liver diseaseSmall intestineHepatic bile saltIntestinal lipid uptakePlasma bile saltsFatty liver diseaseTreatment of NASHColorectal cancer cellsBile saltsConditional knockout modelHuman NASHFatty liverLiver diseaseFXR activationClinical trialsEnterohepatic circulationTranscription factor TCF4Fl/Hepatic levelsBile acidsEndocrine regulatorLipid uptakeIntestinal epitheliumDyrk1b promotes hepatic lipogenesis by bypassing canonical insulin signaling and directly activating mTORC2 in mice
Bhat N, Narayanan A, Fathzadeh M, Kahn M, Zhang D, Goedeke L, Neogi A, Cardone RL, Kibbey RG, Fernandez-Hernando C, Ginsberg HN, Jain D, Shulman G, Mani A. Dyrk1b promotes hepatic lipogenesis by bypassing canonical insulin signaling and directly activating mTORC2 in mice. Journal Of Clinical Investigation 2022, 132: e153724. PMID: 34855620, PMCID: PMC8803348, DOI: 10.1172/jci153724.Peer-Reviewed Original ResearchConceptsDe novo lipogenesisNonalcoholic steatohepatitisInsulin resistanceHepatic lipogenesisElevated de novo lipogenesisNonalcoholic fatty liver diseaseFatty liver diseaseLiver of patientsHepatic glycogen storageHigh-sucrose dietHepatic insulin resistanceFatty acid uptakeMetabolic syndromeLiver diseaseHepatic steatosisTriacylglycerol secretionNovo lipogenesisHepatic insulinTherapeutic targetImpaired activationAcid uptakeGlycogen storageMouse liverLiverLipogenesis
2021
GIMAP5 maintains liver endothelial cell homeostasis and prevents portal hypertension
Drzewiecki K, Choi J, Brancale J, Leney-Greene MA, Sari S, Dalgiç B, Aksu A, Şahin G, Ozen A, Baris S, Karakoc-Aydiner E, Jain D, Kleiner D, Schmalz M, Radhakrishnan K, Zhang J, Hoebe K, Su HC, Pereira JP, Lenardo MJ, Lifton RP, Vilarinho S. GIMAP5 maintains liver endothelial cell homeostasis and prevents portal hypertension. Journal Of Experimental Medicine 2021, 218: e20201745. PMID: 33956074, PMCID: PMC8105721, DOI: 10.1084/jem.20201745.Peer-Reviewed Original ResearchConceptsLiver sinusoidal endothelial cellsPortal hypertensionEndothelial cell homeostasisHepatic endothelial cellsEndothelial cellsLiver diseaseUnexplained portal hypertensionGlobal health problemSinusoidal endothelial cellsCell homeostasisSingle-cell RNA-sequencing analysisHypertensionMouse modelHealth problemsMice resultsGimap5RNA sequence analysisMajor contributorCritical regulatorDiseaseCellsDamaging mutationsHomeostasisDecompensationMorbidity
2020
Paracrine orchestration of intestinal tumorigenesis by a mesenchymal niche
Roulis M, Kaklamanos A, Schernthanner M, Bielecki P, Zhao J, Kaffe E, Frommelt LS, Qu R, Knapp MS, Henriques A, Chalkidi N, Koliaraki V, Jiao J, Brewer JR, Bacher M, Blackburn HN, Zhao X, Breyer RM, Aidinis V, Jain D, Su B, Herschman HR, Kluger Y, Kollias G, Flavell RA. Paracrine orchestration of intestinal tumorigenesis by a mesenchymal niche. Nature 2020, 580: 524-529. PMID: 32322056, PMCID: PMC7490650, DOI: 10.1038/s41586-020-2166-3.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsAntigens, LyArachidonic AcidCarcinogenesisCell Cycle ProteinsCell ProliferationColorectal NeoplasmsCyclooxygenase 2DinoprostoneFemaleFibroblastsHumansIntestinal MucosaIntestinesMaleMembrane ProteinsMesodermMiceNeoplastic Stem CellsOrganoidsParacrine CommunicationReceptors, Prostaglandin E, EP4 SubtypeSingle-Cell AnalysisStem Cell NicheYAP-Signaling ProteinsConceptsSingle-cell RNA-sequencing analysisTumor-initiating stem cellsRNA sequence analysisMesenchymal nicheStem cellsTumor initiationSca-1Hippo pathway effector YAPStem cell functionCell expansionPathway effector YAPMutant stem cellsEpithelial-specific ablationIntestinal stem cellsEarly tumor initiationProstaglandin E2Regenerative reprogrammingNormal epithelial stem cellsParacrine controlTumorigenic programsNiche modelsNuclear localizationTranscriptional activityYAP dephosphorylationEpithelial stem cells
2019
In vivo dynamics of T cells and their interactions with dendritic cells in mouse cutaneous graft-versus-host disease
Morin-Zorman S, Wysocki C, Zhu J, Li H, Zorman S, Matte-Martone C, Kisanga E, McNiff J, Jain D, Gonzalez D, Rothstein DM, Lakkis FG, Haberman A, Shlomchik WD. In vivo dynamics of T cells and their interactions with dendritic cells in mouse cutaneous graft-versus-host disease. Blood Advances 2019, 3: 2082-2092. PMID: 31296496, PMCID: PMC6650737, DOI: 10.1182/bloodadvances.2019000227.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkersCD11c AntigenCell CommunicationDendritic CellsDisease Models, AnimalFluorescent Antibody TechniqueGene ExpressionGenes, ReporterGraft vs Host DiseaseHematopoietic Stem Cell TransplantationHistocompatibility Antigens Class IImmunophenotypingLymphocyte DepletionMiceMice, TransgenicProtein BindingReceptors, Antigen, T-CellSkin DiseasesT-Lymphocyte SubsetsT-LymphocytesTransplantation, HomologousConceptsDonor dendritic cellsCD8 cellsT cellsGVHD lesionsHost diseaseCD4 cellsDendritic cellsAllogeneic hematopoietic stem cell transplantationHematopoietic stem cell transplantationMajority of CD4Dynamics of CD4Stem cell transplantationCutaneous graftAntibody infusionCell transplantationMyeloid cellsIntravital microscopyAcute deletionMajor causeLesionsTarget tissuesCD103CD4InfusionMHCII
2018
Translocation of a gut pathobiont drives autoimmunity in mice and humans
Vieira S, Hiltensperger M, Kumar V, Zegarra-Ruiz D, Dehner C, Khan N, Costa FRC, Tiniakou E, Greiling T, Ruff W, Barbieri A, Kriegel C, Mehta SS, Knight JR, Jain D, Goodman AL, Kriegel MA. Translocation of a gut pathobiont drives autoimmunity in mice and humans. Science 2018, 359: 1156-1161. PMID: 29590047, PMCID: PMC5959731, DOI: 10.1126/science.aar7201.Peer-Reviewed Original ResearchConceptsGut pathobiontAutoimmune-prone miceMurine findingsIntramuscular vaccinePathogenic autoantibodiesLiver biopsyAutoimmune responseAutoimmune patientsAntibiotic treatmentT cellsImmune diseasesAutoimmunitySusceptible humansPathobiontsSystemic tissuesHuman hepatocytesAutoantibodiesMortalityMiceCocultureHepatocytesGenetic backgroundTissueBiopsyPatients
2017
Bile acids initiate cholestatic liver injury by triggering a hepatocyte-specific inflammatory response
Cai SY, Ouyang X, Chen Y, Soroka CJ, Wang J, Mennone A, Wang Y, Mehal WZ, Jain D, Boyer JL. Bile acids initiate cholestatic liver injury by triggering a hepatocyte-specific inflammatory response. JCI Insight 2017, 2: e90780. PMID: 28289714, PMCID: PMC5333973, DOI: 10.1172/jci.insight.90780.Peer-Reviewed Original ResearchConceptsLiver injuryInflammatory responseBile acid-induced liver injuryCholestatic liver injuryInflammatory liver injuryProinflammatory cytokine expressionCholestatic liver diseaseBile duct ligationVivo mouse modelHepatic infiltrationInflammatory injurySerum aminotransferasesLiver diseaseCholestatic patientsCytokine expressionChemokine inductionPathophysiologic concentrationsNeutrophil chemotaxisDuct ligationPathophysiologic levelsMouse modelNew therapiesInnate immunityInjuryPeriportal areas
2016
αvβ6 Integrin Promotes Castrate-Resistant Prostate Cancer through JNK1-Mediated Activation of Androgen Receptor
Lu H, Wang T, Li J, Fedele C, Liu Q, Zhang J, Jiang Z, Jain D, Iozzo RV, Violette SM, Weinreb PH, Davis RJ, Gioeli D, FitzGerald TJ, Altieri DC, Languino LR. αvβ6 Integrin Promotes Castrate-Resistant Prostate Cancer through JNK1-Mediated Activation of Androgen Receptor. Cancer Research 2016, 76: 5163-5174. PMID: 27450452, PMCID: PMC5012867, DOI: 10.1158/0008-5472.can-16-0543.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, NeoplasmCell Line, TumorDisease Models, AnimalFlow CytometryFluorescent Antibody TechniqueGene Knockdown TechniquesHumansImmunohistochemistryIntegrinsMaleMiceMice, KnockoutMitogen-Activated Protein Kinase 8Prostatic Neoplasms, Castration-ResistantReceptors, AndrogenSignal TransductionConceptsΑvβ6 expressionAndrogen receptorProstate cancerΑvβ6 integrinCastrate-resistant prostate cancerProstate cancer mouse modelAbsence of androgenFurther clinical developmentProstate cancer therapyCancer mouse modelNormal prostatic epitheliumProstate cancer progressionΑv-containing integrinsMajor therapeutic targetUpregulation of survivinActivation of JNK1Androgen ablationDownstream kinase activationMechanisms of resistanceProstatic adenocarcinomaInvolvement of p38Preclinical resultsMouse modelProstatic epitheliumClinical development
2014
Glucocerebrosidase 2 gene deletion rescues type 1 Gaucher disease
Mistry PK, Liu J, Sun L, Chuang WL, Yuen T, Yang R, Lu P, Zhang K, Li J, Keutzer J, Stachnik A, Mennone A, Boyer JL, Jain D, Brady RO, New MI, Zaidi M. Glucocerebrosidase 2 gene deletion rescues type 1 Gaucher disease. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 4934-4939. PMID: 24639522, PMCID: PMC3977292, DOI: 10.1073/pnas.1400768111.Peer-Reviewed Original ResearchConceptsType 1 Gaucher's diseaseBone formation defectGaucher diseaseSerum ceramide levelsBone formation rateEnzyme replacement therapyViable therapeutic targetGD1 patientsGBA deficiencyEnhanced elevationTherapeutic targetBone volumeMononuclear phagocytesClinical phenotypeGBA geneConditional deletionBioactive lipidsSphingosine levelsDevelopment of inhibitorsCeramide levelsLysosomal glucocerebrosidasePatientsNanomolar concentrationsDiseaseMice
2012
Gaucher disease gene GBA functions in immune regulation
Liu J, Halene S, Yang M, Iqbal J, Yang R, Mehal WZ, Chuang WL, Jain D, Yuen T, Sun L, Zaidi M, Mistry PK. Gaucher disease gene GBA functions in immune regulation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 10018-10023. PMID: 22665763, PMCID: PMC3382552, DOI: 10.1073/pnas.1200941109.Peer-Reviewed Original ResearchConceptsGaucher diseaseHematopoietic stem cellsImmune regulationDisease severityGBA geneWidespread immune dysregulationB cell recruitmentPeripheral lymphoid organsT cell maturationLyso-GL1Immune dysregulationT helperImmune defectsTh2 cytokinesEarly thymic progenitorsLymphoid organsAntigen presentationGBA deficiencyGBA mutationsSevere diseaseClassic manifestationsClinical observationsGCase deficiencyBone marrowMature thymocytes
2011
Enhancing alloreactivity does not restore GVHD induction but augments skin graft rejection by CD4+ effector memory T cells
Anderson BE, Tang AL, Wang Y, Froicu M, Rothstein D, McNiff JM, Jain D, Demetris AJ, Farber DL, Shlomchik WD, Shlomchik MJ. Enhancing alloreactivity does not restore GVHD induction but augments skin graft rejection by CD4+ effector memory T cells. European Journal Of Immunology 2011, 41: 2782-2792. PMID: 21660940, PMCID: PMC3517133, DOI: 10.1002/eji.201141678.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsCD4-Positive T-LymphocytesDisease Models, AnimalGenes, T-Cell ReceptorGraft RejectionGraft vs Host DiseaseHematopoietic Stem Cell TransplantationHumansImmunologic MemoryIsoantigensLymphocyte ActivationMicePostoperative ComplicationsSkin TransplantationT-Cell Antigen Receptor SpecificityT-Lymphocyte SubsetsConceptsEffector memory T cellsMemory T cellsSkin graft rejectionLymphopenia-induced proliferationT cellsMild GVHDAlloreactive clonesGraft rejectionAllogeneic hematopoietic stem cell transplantationHematopoietic stem cell transplantationT cell receptor repertoireGVHD effector cellsDonor T cellsStem cell transplantationDiverse T cell receptor repertoireNaive T cellsRapid skin graft rejectionAlloreactive repertoireGVHD inductionLimited GVHDHost diseaseLeukemia effectEffector cellsCell transplantationSyngeneic recipientsGraft-versus-Host Disease Is Independent of Innate Signaling Pathways Triggered by Pathogens in Host Hematopoietic Cells
Li H, Matte-Martone C, Tan HS, Venkatesan S, McNiff J, Demetris AJ, Jain D, Lakkis F, Rothstein D, Shlomchik WD. Graft-versus-Host Disease Is Independent of Innate Signaling Pathways Triggered by Pathogens in Host Hematopoietic Cells. The Journal Of Immunology 2011, 186: 230-241. PMID: 21098219, PMCID: PMC5822434, DOI: 10.4049/jimmunol.1002965.Peer-Reviewed Original ResearchConceptsT cell responsesHost APCsHost diseaseAPC maturationT cellsAllogeneic hematopoietic stem cell transplantationAlloreactive donor T cellsCell responsesAdaptive T cell responsesHematopoietic stem cell transplantationHost hematopoietic cellsHost IL-12Donor T cellsAlloreactive T cellsStem cell transplantationT cell productionType I IFNInnate signaling pathwaysPattern recognition receptorsHematopoietic cellsMyD88/IL-12Cell transplantationIL-1βInflammatory cytokines
2010
Glucocerebrosidase gene-deficient mouse recapitulates Gaucher disease displaying cellular and molecular dysregulation beyond the macrophage
Mistry PK, Liu J, Yang M, Nottoli T, McGrath J, Jain D, Zhang K, Keutzer J, Chuang WL, Mehal WZ, Zhao H, Lin A, Mane S, Liu X, Peng YZ, Li JH, Agrawal M, Zhu LL, Blair HC, Robinson LJ, Iqbal J, Sun L, Zaidi M. Glucocerebrosidase gene-deficient mouse recapitulates Gaucher disease displaying cellular and molecular dysregulation beyond the macrophage. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 19473-19478. PMID: 20962279, PMCID: PMC2984187, DOI: 10.1073/pnas.1003308107.Peer-Reviewed Original ResearchConceptsType 1 Gaucher diseaseThymic T cellsGene-deficient miceOsteoblastic bone formationWorthwhile therapeutic targetDendritic cellsSevere osteoporosisAutoimmune diseasesWidespread dysfunctionCytokine measurementsT cellsCell lineagesParkinson's diseaseTherapeutic targetGBA1 geneMononuclear phagocytesGaucher diseaseGlucocerebrosidase deficiencyMolecular dysregulationDiseaseInhibitory effectBone formationMultiple cell lineagesMesenchymal cell lineagesMacrophagesDantrolene mitigates caerulein-induced pancreatitis in vivo in mice
Orabi AI, Shah AU, Ahmad MU, Choo-Wing R, Parness J, Jain D, Bhandari V, Husain SZ. Dantrolene mitigates caerulein-induced pancreatitis in vivo in mice. AJP Gastrointestinal And Liver Physiology 2010, 299: g196-g204. PMID: 20448143, PMCID: PMC2904115, DOI: 10.1152/ajpgi.00498.2009.Peer-Reviewed Original ResearchMeSH KeywordsAmylasesAnimalsApoptosisCalcium Channel BlockersCalcium SignalingCeruletideCytoprotectionDantroleneDisease Models, AnimalEnzyme ActivationFluorescent Antibody TechniqueIn Situ Nick-End LabelingMaleMiceMice, Inbred C57BLMicroscopy, ElectronPancreasPancreatitisRyanodine Receptor Calcium Release ChannelSeverity of Illness IndexTime FactorsTrypsinConceptsPancreatic trypsin activityCaerulein-induced pancreatitisRyanodine receptorAcinar cellsMouse pancreatic sectionsHigh-risk settingsTUNEL-positive cellsLater time pointsRyR inhibitor dantroleneDantrolene pretreatmentHistological severityAcute pancreatitisPancreatic acinar cellsInflammatory disordersProphylactic treatmentRyR inhibitionSerum amylasePancreatitis inductionPancreatic sectionsPancreatitisAdequate treatmentTrypsin activityEarly markerCaerulein hyperstimulationUltrastructural derangementsRecipient B Cells Are Not Required for Graft-Versus-Host Disease Induction
Matte-Martone C, Wang X, Anderson B, Jain D, Demetris AJ, McNiff J, Shlomchik MJ, Shlomchik WD. Recipient B Cells Are Not Required for Graft-Versus-Host Disease Induction. Transplantation And Cellular Therapy 2010, 16: 1222-1230. PMID: 20338255, PMCID: PMC3135976, DOI: 10.1016/j.bbmt.2010.03.015.Peer-Reviewed Original ResearchConceptsRecipient B cellsAntigen presenting cellsB cellsAllogeneic hematopoietic stem cell transplantationB cell-deficient recipientsImportant antigen presenting cellsRecipient antigen presenting cellsAllogeneic bone marrow transplantationHematopoietic stem cell transplantationCD8-mediated GVHDHost disease inductionB-cell depletionAntibody-mediated depletionHost B cellsCD20 monoclonal antibodyStem cell transplantationT cell responsesBone marrow transplantationGraft-VersusAPC subsetsHost diseaseMarrow transplantationCell depletionCell transplantationPresenting cells
2009
Protease activation during in vivo pancreatitis is dependent on calcineurin activation
Shah AU, Sarwar A, Orabi AI, Gautam S, Grant WM, Park AJ, Shah AU, Liu J, Mistry PK, Jain D, Husain SZ. Protease activation during in vivo pancreatitis is dependent on calcineurin activation. AJP Gastrointestinal And Liver Physiology 2009, 297: g967-g973. PMID: 20501444, PMCID: PMC2777459, DOI: 10.1152/ajpgi.00181.2009.Peer-Reviewed Original ResearchConceptsAcinar cellsProtease activationDependent phosphatase calcineurinHourly intraperitoneal injectionsCourse of pancreatitisAcinar cell vacuolizationCholecystokinin analogue caeruleinPhosphatase calcineurinHistological severityMyeloperoxidase activityPancreatic acinar cellsAcute pancreatitisIL-6Inhibitor FK506Pancreatic edemaSerum amylaseIntraperitoneal injectionPancreatitis inductionPancreatitis severityCalcineurin activationPancreatitisPathological riseCell vacuolizationDigestive proenzymesPremature activationCentral Memory CD8+ T Cells Induce Graft-versus-Host Disease and Mediate Graft-versus-Leukemia
Zheng H, Matte-Martone C, Jain D, McNiff J, Shlomchik WD. Central Memory CD8+ T Cells Induce Graft-versus-Host Disease and Mediate Graft-versus-Leukemia. The Journal Of Immunology 2009, 182: 5938-5948. PMID: 19414745, PMCID: PMC9844260, DOI: 10.4049/jimmunol.0802212.Peer-Reviewed Original ResearchConceptsMemory T cellsT cellsHost diseaseAllogeneic hemopoietic stem cell transplantationChronic phase chronic myelogenous leukemiaFunctional T-cell memoryMultiple minor histocompatibility AgsBALB/c recipientsEffector memory T cellsHemopoietic stem cell transplantationCentral memory T cellsNonmalignant host tissuesCentral memory CD8Donor T cellsMinor histocompatibility AgT-cell reconstitutionStem cell transplantationT cell memoryNaive T cellsAlphabeta T cellsChronic myelogenous leukemiaC recipientsClinical GVHDHistological diseaseLeukemia effect
2008
Effects of donor T-cell trafficking and priming site on graft-versus-host disease induction by naive and memory phenotype CD4 T cells
Anderson BE, Taylor PA, McNiff JM, Jain D, Demetris AJ, Panoskaltsis-Mortari A, Ager A, Blazar BR, Shlomchik WD, Shlomchik MJ. Effects of donor T-cell trafficking and priming site on graft-versus-host disease induction by naive and memory phenotype CD4 T cells. Blood 2008, 111: 5242-5251. PMID: 18285547, PMCID: PMC2384145, DOI: 10.1182/blood-2007-09-107953.Peer-Reviewed Original ResearchConceptsSecondary lymphoid tissuesT cellsMemory phenotype CD4 T cellsEffector memory T cellsAllogeneic stem cell transplantationHost disease inductionCD4 T cellsMemory T cellsStem cell transplantationNaive T cellsT cell traffickingGVHD initiationMild GVHDHost diseaseTransplant recipientsTumor effectCell transplantationLymphoid tissueGVHDDisease inductionImmune responseCD62LCCR7Major causeGraftCD8+ but not CD4+ T cells require cognate interactions with target tissues to mediate GVHD across only minor H antigens, whereas both CD4+ and CD8+ T cells require direct leukemic contact to mediate GVL
Matte-Martone C, Liu J, Jain D, McNiff J, Shlomchik WD. CD8+ but not CD4+ T cells require cognate interactions with target tissues to mediate GVHD across only minor H antigens, whereas both CD4+ and CD8+ T cells require direct leukemic contact to mediate GVL. Blood 2008, 111: 3884-3892. PMID: 18223170, PMCID: PMC2275040, DOI: 10.1182/blood-2007-11-125294.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesDisease Models, AnimalGraft vs Host DiseaseGraft vs Leukemia EffectHistocompatibility Antigens Class IHistocompatibility Antigens Class IIHumansLeukemia, Myelogenous, Chronic, BCR-ABL PositiveMiceMice, KnockoutMinor Histocompatibility AntigensReceptors, Antigen, T-CellStem Cell TransplantationTransplantation ChimeraTransplantation, HomologousConceptsCD4 cellsT cellsT cell antigen receptorAllogeneic stem cell transplantationMajor histocompatibility complex class IDirect cytolytic actionDistinct effector mechanismsDonor CD4 cellsDonor T cellsStem cell transplantationHistocompatibility complex class IMinor H antigensClass II moleculesComplex class IHost diseaseBCR-ABL cDNAGVHDEffector mechanismsMouse modelCML cellsBone marrowCognate interactionNoncytolytic pathwaysCD8Cytolytic action