2013
c‐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
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 macrophagesRoles 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
2009
Cytolytic 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
IL-17 contributes to CD4-mediated graft-versus-host disease
Kappel L, Goldberg G, King C, Suh D, Smith O, Ligh C, Holland A, Grubin J, Mark N, Liu C, Iwakura Y, Heller G, van den Brink M. IL-17 contributes to CD4-mediated graft-versus-host disease. Blood 2008, 113: 945-952. PMID: 18931341, PMCID: PMC2630280, DOI: 10.1182/blood-2008-08-172155.Peer-Reviewed Original ResearchConceptsRecipients of ILT cellsGVHD mortalityHost diseaseIL-17Proinflammatory cytokinesAllogeneic bone marrow transplantAllogeneic BMT modelIL-17 contributesDonor T cellsBone marrow transplantWhole T cellsT-cell recipientsAcute graftGVHD developmentGVT activityAllograft rejectionTh17 cellsIL-17FIL-22Interleukin-17Marrow transplantAutoimmune diseasesTh1 cellsLymphoid organsCombined Th2 cytokine deficiency in donor T cells aggravates experimental acute graft-vs-host disease
Tawara I, Maeda Y, Sun Y, Lowler K, Liu C, Toubai T, McKenzie A, Reddy P. Combined Th2 cytokine deficiency in donor T cells aggravates experimental acute graft-vs-host disease. Experimental Hematology 2008, 36: 988-996. PMID: 18410989, PMCID: PMC2603625, DOI: 10.1016/j.exphem.2008.02.010.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAnimalsBone Marrow TransplantationCD4-Positive T-LymphocytesCell ProliferationDisease Models, AnimalEnzyme-Linked Immunosorbent AssayFemaleFlow CytometryGraft vs Host DiseaseImmunologic TestsInterleukin-2 Receptor alpha SubunitInterleukinsMajor Histocompatibility ComplexMiceMice, Inbred BALB CMice, Inbred C57BLSurvival RateTh2 CellsT-LymphocytesTransplantation, HomologousConceptsDonor T cellsT cellsWT T cellsTh2 cytokinesAcute graftAllogeneic bone marrow transplantationAllogeneic antigen-presenting cellsT cell proliferative responsesAnti-CD3 monoclonal antibodyEnhanced T cell proliferationExperimental acute graftNumber of immunoregulatoryTarget organ damageTh2 cytokine secretionBone marrow transplantationT helper 1Antigen-presenting cellsWild-type T cellsT cell proliferationGreater clinical severityBALB/cB6 recipientsGVHD mortalityHost diseaseIL-17
2007
CCR1/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 relapseLymphopenia-induced proliferation of donor T cells reduces their capacity for causing acute graft-versus-host disease
Maeda Y, Tawara I, Teshima T, Liu C, Hashimoto D, Matsuoka K, Tanimoto M, Reddy P. Lymphopenia-induced proliferation of donor T cells reduces their capacity for causing acute graft-versus-host disease. Experimental Hematology 2007, 35: 274-286. PMID: 17258076, DOI: 10.1016/j.exphem.2006.10.010.Peer-Reviewed Original ResearchConceptsAllogeneic bone marrow transplantationDonor T cellsBone marrow transplantationLymphopenia-induced proliferationNaïve T cellsT cellsHost diseaseAcute GVHD severityAnti-tumor immunityT cell subsetsPhenotype T cellsMurine experimental modelAnti-tumor functionAcute graftGVHD mortalitySevere GVHDGVHD severityAllograft rejectionMarrow transplantationCell depletionCell subsetsGVHDBiochemical parametersExperimental modelGraft
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 mortalitySuberoylanilide hydroxamic acid modulates the innate and allostimulatory responses of dendritic cells and regulates experimental acute graft-versus-host disease
Reddy P, Maeda Y, Lowler K, Liu C, Dinarello C, Ferrara J. Suberoylanilide hydroxamic acid modulates the innate and allostimulatory responses of dendritic cells and regulates experimental acute graft-versus-host disease. Transplantation And Cellular Therapy 2005, 11: 48. DOI: 10.1016/j.bbmt.2004.12.142.Peer-Reviewed Original ResearchStimulation of Host NKT Cells by Synthetic Glycolipid Regulates Acute Graft-versus-Host Disease by Inducing Th2 Polarization of Donor T Cells
Hashimoto D, Asakura S, Miyake S, Yamamura T, Van Kaer L, Liu C, Tanimoto M, Teshima T. Stimulation of Host NKT Cells by Synthetic Glycolipid Regulates Acute Graft-versus-Host Disease by Inducing Th2 Polarization of Donor T Cells. The Journal Of Immunology 2005, 174: 551-556. PMID: 15611282, DOI: 10.4049/jimmunol.174.1.551.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CD1Antigens, CD1dBone Marrow TransplantationEnzyme-Linked Immunosorbent AssayFemaleFlow CytometryGalactosylceramidesGlycolipidsGraft vs Host DiseaseMiceMice, KnockoutSTAT6 Transcription FactorTh2 CellsT-Lymphocyte SubsetsT-LymphocytesTrans-ActivatorsTumor Necrosis Factor-alphaConceptsHost NKT cellsDonor T cellsNKT cellsT cellsTh2 polarizationAcute GVHDAcute graftHost diseaseAlpha-GalCerAllogeneic bone marrow transplantationImmunoregulatory T-cell populationsMortality of GVHDTh2 cytokine responsesSerum TNF-alphaNKT cell ligandBone marrow transplantationSTAT6-dependent mechanismT cell populationsNKT ligandCytokine responsesMarrow transplantationIL-4Recipient miceTNF-alphaGVHD
2004
CCR1 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 GVHDBoth perforin and Fas ligand are required for the regulation of alloreactive CD8+ T cells during acute graft-versus-host disease
Maeda Y, Levy R, Reddy P, Liu C, Clouthier S, Teshima T, Ferrara J. Both perforin and Fas ligand are required for the regulation of alloreactive CD8+ T cells during acute graft-versus-host disease. Blood 2004, 105: 2023-2027. PMID: 15466930, DOI: 10.1182/blood-2004-08-3036.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAnimalsBone Marrow TransplantationCD8-Positive T-LymphocytesCell Culture TechniquesFas Ligand ProteinGraft vs Host DiseaseHistocompatibilityHistocompatibility Antigens Class ILymphocyte TransfusionMembrane GlycoproteinsMiceMice, Inbred StrainsModels, AnimalPerforinPore Forming Cytotoxic ProteinsTransplantation, HomologousConceptsT cellsHost diseaseAllogeneic bone marrow transplantationT cell-mediated cytotoxicityTumor necrosis factor alphaMajor histocompatibility complex class IGreater serum levelsDonor T cellsBone marrow transplantationCell-mediated cytotoxicityHistocompatibility complex class IWild-type T cellsNecrosis factor alphaComplex class ILethal GVHDAcute graftAlloreactive CD8Histopathologic damageMarrow transplantationSerum levelsAlloantigen stimulationIrradiated murine modelFactor alphaCD8Murine modelParadoxical effects of interleukin-18 on the severity of acute graft-versus-host disease mediated by CD4+ and CD8+ T-cell subsets after experimental allogeneic bone marrow transplantation
Min C, Maeda Y, Lowler K, Liu C, Clouthier S, Lofthus D, Weisiger E, Ferrara J, Reddy P. Paradoxical effects of interleukin-18 on the severity of acute graft-versus-host disease mediated by CD4+ and CD8+ T-cell subsets after experimental allogeneic bone marrow transplantation. Blood 2004, 104: 3393-3399. PMID: 15280194, DOI: 10.1182/blood-2004-02-0763.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAnimalsAntibodies, MonoclonalApoptosisBone Marrow TransplantationCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCytokinesDisease Models, AnimalFemaleGraft vs Host DiseaseHistocompatibility Antigens Class IHistocompatibility Antigens Class IIInterleukin-18Interleukin-18 Receptor alpha SubunitMiceMice, Inbred C57BLReceptors, InterleukinReceptors, Interleukin-18Severity of Illness IndexT-Lymphocytes, CytotoxicTransplantation, HomologousConceptsAllogeneic bone marrow transplantationBone marrow transplantationExperimental allogeneic bone marrow transplantationDonor T cellsIL-18T cellsAcute GVHDAcute graftHost diseaseInterleukin-18Marrow transplantationClinical allogeneic bone marrow transplantationMajor histocompatibility complex class IIHistocompatibility complex class IIEndogenous IL-18Experimental acute graftT cell subsetsParadoxical effectFas-dependent mannerLess GVHDCytotoxic functionHistopathologic parametersGVHDClass IIFas expressionHost Dendritic Cells Alone Are Sufficient to Initiate Acute Graft-versus-Host Disease
Duffner U, Maeda Y, Cooke K, Reddy P, Ordemann R, Liu C, Ferrara J, Teshima T. Host Dendritic Cells Alone Are Sufficient to Initiate Acute Graft-versus-Host Disease. The Journal Of Immunology 2004, 172: 7393-7398. PMID: 15187116, DOI: 10.4049/jimmunol.172.12.7393.Peer-Reviewed Original ResearchConceptsHost dendritic cellsDendritic cellsB cellsT cellsAcute GVHDHost diseaseHost-derived dendritic cellsLethal acute GVHDAllogeneic dendritic cellsII-deficient miceMHC class IIMHC class IAcute graftChimeric recipientsHost APCsAPC subsetsAlloantigen expressionGVHDMHC classClass IIClass IRobust proliferationSelective targetingGraftDiseaseHistone deacetylase inhibitor suberoylanilide hydroxamic acid reduces acute graft-versus-host disease and preserves graft-versus-leukemia effect
Reddy P, Maeda Y, Hotary K, Liu C, Reznikov L, Dinarello C, Ferrara J. Histone deacetylase inhibitor suberoylanilide hydroxamic acid reduces acute graft-versus-host disease and preserves graft-versus-leukemia effect. Proceedings Of The National Academy Of Sciences Of The United States Of America 2004, 101: 3921-3926. PMID: 15001702, PMCID: PMC374345, DOI: 10.1073/pnas.0400380101.Peer-Reviewed Original ResearchConceptsBone marrow transplantationSuberoylanilide hydroxamic acidAdministration of SAHAProinflammatory cytokinesGVL activityAcute graftHost diseaseHost antigensTime of BMTAllogeneic bone marrow transplantationDonor/recipient combinationsEffects of SAHACytotoxic T cell responsesCytotoxic responseBeneficial GVL effectLeukemia-free survivalT cell proliferativeHistone deacetylase inhibitor suberoylanilide hydroxamic acidT cell responsesVehicle-treated animalsGastrointestinal tract integrityInhibitor suberoylanilide hydroxamic acidHistone deacetylase inhibitionAcute GVHDGVL effect
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 recipientsImpaired thymic negative selection causes autoimmune graft-versus-host disease
Teshima T, Reddy P, Liu C, Williams D, Cooke K, Ferrara J. Impaired thymic negative selection causes autoimmune graft-versus-host disease. Blood 2003, 102: 429-435. PMID: 12663438, DOI: 10.1182/blood-2003-01-0266.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsAutoimmune DiseasesBone Marrow TransplantationCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCells, CulturedClonal DeletionDendritic CellsEpithelial CellsFemaleGraft vs Host DiseaseInflammation MediatorsInterleukin-1MiceMice, Inbred C57BLRadiation ChimeraRadiation ToleranceSelf ToleranceSkinSpleenThymectomyThymus GlandT-Lymphocyte SubsetsTumor Necrosis Factor-alphaVisceraConceptsThymic negative selectionSystemic autoimmune diseaseAntigen-presenting cellsAutoimmune diseasesHost diseaseT cellsAutoreactive T cell repertoireClass IIThymic antigen-presenting cellsMajor histocompatibility complex class IIHistocompatibility complex class IIImpaired negative selectionLethal autoimmune diseaseBone marrow chimerasPeripheral regulatory mechanismsT cell repertoireMHC class IIMHC class INegative selectionAcute graftAcute GVHDAutoimmune graftPeripheral CD4Adoptive transferNaive mice