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
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 lineagesMacrophages
2009
Central 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
Redundant Mechanisms for Dendritic Cell Activation in GVHD Induction: Signalings Via TLRs, TNF-α, IL-1 and CD40 Are Not Required
Li H, Matte-Martone C, Demetris A, McNiff J, Jain D, Shlomchik W. Redundant Mechanisms for Dendritic Cell Activation in GVHD Induction: Signalings Via TLRs, TNF-α, IL-1 and CD40 Are Not Required. Blood 2008, 112: 3509. DOI: 10.1182/blood.v112.11.3509.3509.Peer-Reviewed Original ResearchHost antigen-presenting cellsAntigen-presenting cellsToll-like receptorsDC maturation signalsDonor T cellsDendritic cellsT cellsT cell activationMaturation signalsCell activationGVHD inductionHistologic GVHDMyD88/DC maturationAPC maturationIL-1Alloreactive donor T cellsAlloreactive T cell activationAdaptive T cell responsesAllogeneic stem cell transplantationHost hematopoietic cellsTNFR1/R2WT B6 miceDendritic cell activationT cell primingEffects 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
2007
Effector memory CD4+ T cells mediate graft-versus-leukemia without inducing graft-versus-host disease
Zheng H, Matte-Martone C, Li H, Anderson BE, Venketesan S, Tan H, Jain D, McNiff J, Shlomchik WD. Effector memory CD4+ T cells mediate graft-versus-leukemia without inducing graft-versus-host disease. Blood 2007, 111: 2476-2484. PMID: 18045967, PMCID: PMC2234071, DOI: 10.1182/blood-2007-08-109678.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone Marrow TransplantationCD4-Positive T-LymphocytesGraft vs Host DiseaseGraft vs Leukemia EffectHematopoietic Stem Cell TransplantationHistocompatibility TestingImmunologic MemoryLeukemia, Myelogenous, Chronic, BCR-ABL PositiveLymphocyte TransfusionMajor Histocompatibility ComplexMiceTransplantation, HomologousConceptsDonor T cellsT cellsHost diseaseAllogeneic hematopoietic stem cell transplantationFunctional T-cell memoryPerforin-deficient T cellsT-cell-depleted allograftsEffector memory T cellsHematopoietic stem cell transplantationDirect cytolytic functionNonmalignant host tissuesEffector memory CD4Memory T cellsStem cell transplantationT cell memoryBlast crisis chronic myelogenous leukemiaRelevant mouse modelChronic myelogenous leukemiaApplicable cell therapyRecipient alloantigensImmune reconstitutionLeukemia effectMemory CD4Chronic phaseCell transplantation
2005
CD8+ Central Memory T Cells Mediate Graft-Versus-Host Disease Although Retain Graft-Versus-Leukemia Effect.
Zheng H, Matte C, Anderson B, Venkatesan S, Jain D, Shlomchik M, Shlomchik W. CD8+ Central Memory T Cells Mediate Graft-Versus-Host Disease Although Retain Graft-Versus-Leukemia Effect. Blood 2005, 106: 1312. DOI: 10.1182/blood.v106.11.1312.1312.Peer-Reviewed Original ResearchCD8 cellsMemory T cellsMore weight lossCell recipientsT cellsCM cellsWeight lossGraft-VersusHistologic GVHDLess weight lossEffector functionsBALB/c recipientsEffector memory T cellsCentral memory T cellsDay 16Central memory TClear histologic evidencePeriportal inflammatory infiltrationReconstitution of immunityDonor T cellsTime pointsMost time pointsDonor BMEarly time pointsEffective GVLCD8+ but Not CD4+ T Cells Require Cognate Interactions with Target Tissues To Mediate GVHD across Only Minor H Antigens but CD4+ and CD8+ T Cells Both Require Direct Leukemic Contact for GVL.
Shlomchik W, Matte C, Liu J, Jain D, McNiff J. CD8+ but Not CD4+ T Cells Require Cognate Interactions with Target Tissues To Mediate GVHD across Only Minor H Antigens but CD4+ and CD8+ T Cells Both Require Direct Leukemic Contact for GVL. Blood 2005, 106: 580. DOI: 10.1182/blood.v106.11.580.580.Peer-Reviewed Original ResearchCD8-mediated GVHDDirect cognate interactionT cellsSecond transplantCD4 cellsCD8 cellsHost antigensCognate interactionMHCII expressionBone marrowDonor CD4 cellsDonor-derived APCsTarget tissuesT-cell releaseAlloreactive T cellsBone marrow chimerasMinor H antigensCognate T cellsChimeric recipientsDonor BMGVHD lethalityHistologic GVHDHost APCsLess GVHDLeukemic expression
2004
Distinct roles for donor- and host-derived antigen-presenting cells and costimulatory molecules in murine chronic graft-versus-host disease: requirements depend on target organ
Anderson BE, McNiff JM, Jain D, Blazar BR, Shlomchik WD, Shlomchik MJ. Distinct roles for donor- and host-derived antigen-presenting cells and costimulatory molecules in murine chronic graft-versus-host disease: requirements depend on target organ. Blood 2004, 105: 2227-2234. PMID: 15522961, DOI: 10.1182/blood-2004-08-3032.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigen-Presenting CellsAntigens, CDB7-1 AntigenB7-2 AntigenBone Marrow TransplantationCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesChronic DiseaseDisease Models, AnimalGraft vs Host DiseaseIntestinal DiseasesMembrane GlycoproteinsMiceMice, Inbred BALB COrgan SpecificitySkin DiseasesTransplantation, HomologousConceptsHost antigen-presenting cellsAntigen-presenting cellsDonor antigen-presenting cellsChronic GVHDAcute GVHDHost diseaseAPC requirementsHost-derived antigen-presenting cellsAllogeneic stem cell transplantationMurine chronic graftCD8 T cellsStem cell transplantationChronic graftGVHD therapyCell transplantationChronic formCostimulatory moleculesGVHDT cellsTarget organsAPC functionCD80/86Pathogenesis mechanismsCD4Graft