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
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
2011
Prospective Evaluation of Acute Graft-Versus-Host Disease
Aslanian H, Chander B, Robert M, Cooper D, Proctor D, Seropian S, Jain D. Prospective Evaluation of Acute Graft-Versus-Host Disease. Digestive Diseases And Sciences 2011, 57: 720-725. PMID: 22011927, DOI: 10.1007/s10620-011-1938-x.Peer-Reviewed Original ResearchConceptsAcute GVHDHost diseaseLower endoscopyRectal biopsyDiagnostic yieldGastrointestinal tractAllogeneic bone marrow transplantationAcute Graft-VersusCases of GVHDLower gastrointestinal involvementOptimal endoscopic approachDiagnosis of GVHDNon-specific symptomsStem cell transplantationBone marrow transplantationUpper gastrointestinal tractLower gastrointestinal tractUpper intestinal tractMajority of casesColonic GVHDGastrointestinal GVHDGastrointestinal involvementGraft-VersusGVHD casesIntestinal GVHDEnhancing 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
Recipient 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
Mycophenolate Mofetil-induced Colitis in Children
Phatak UP, Seo-Mayer P, Jain D, Selbst M, Husain S, Pashankar DS. Mycophenolate Mofetil-induced Colitis in Children. Journal Of Clinical Gastroenterology 2009, 43: 967-969. PMID: 19609219, DOI: 10.1097/mcg.0b013e3181a8754d.Peer-Reviewed Original ResearchConceptsMycophenolate mofetilSevere colitisMild gastrointestinal side effectsPediatric renal transplant patientsWithdrawal of MMFMaintenance of immunosuppressionRenal transplant patientsInflammatory bowel diseaseGastrointestinal side effectsCause of diarrheaMMF therapyHost diseaseTransplant patientsBowel diseaseColonic biopsiesHistologic featuresPatient 1Patient 2Histologic findingsComplete resolutionSide effectsColitisPatientsCausal associationMofetilCentral 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 effectSpectrum of histologic changes in colonic biopsies in patients treated with mycophenolate mofetil
Selbst MK, Ahrens WA, Robert ME, Friedman A, Proctor DD, Jain D. Spectrum of histologic changes in colonic biopsies in patients treated with mycophenolate mofetil. Modern Pathology 2009, 22: 737-743. PMID: 19329937, DOI: 10.1038/modpathol.2009.44.Peer-Reviewed Original ResearchConceptsSolid organ transplant patientsSelf-limited colitisMycophenolate mofetilInflammatory bowel diseaseOrgan transplant patientsColonic biopsiesHistologic changesHost diseaseGastrointestinal symptomsTransplant patientsBowel diseaseArchitectural distortionMycophenolate mofetil usePaneth cell metaplasiaSolid organ transplantationMofetil useInflammatory bowelMucin depletionCell metaplasiaImmunosuppressive agentsInflammatory infiltrateHistologic patternCase reportHistologic spectrumDiagnostic difficulties
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
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
2004
Distinct Roles for Donor and Host Antigen Presenting Cells and Costimulatory Molecules in Murine Chronic Graft-Vs-Host Disease: Requirements Depend on Target Organ.
Anderson B, McNiff J, Jain D, Blazar B, Shlomchik W, Shlomchik M. Distinct Roles for Donor and Host Antigen Presenting Cells and Costimulatory Molecules in Murine Chronic Graft-Vs-Host Disease: Requirements Depend on Target Organ. Blood 2004, 104: 3059. DOI: 10.1182/blood.v104.11.3059.3059.Peer-Reviewed Original ResearchChronic GVHDCutaneous chronic GVHDHost APCsCD4 cellsWT BMDonor APCsAcute GVHDHost diseaseRecipient APCsAPC requirementsHost antigen presenting cellsAllogeneic stem cell transplantationChronic Graft-vsDonor CD4 cellsPre-transplant weightDonor T cellsStem cell transplantationCostimulatory molecules CD80Antigen presenting cellsSite of diseaseChimeric recipientsCutaneous GVHDDonor BMGraft-vsGVHD preventionDistinct 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 mechanismsCD4GraftTarget Antigens Determine Graft-versus-Host Disease Phenotype
Kaplan DH, Anderson BE, McNiff JM, Jain D, Shlomchik MJ, Shlomchik WD. Target Antigens Determine Graft-versus-Host Disease Phenotype. The Journal Of Immunology 2004, 173: 5467-5475. PMID: 15494494, DOI: 10.4049/jimmunol.173.9.5467.Peer-Reviewed Original ResearchConceptsHost diseaseSkin diseasesBALB/c recipientsAllogeneic stem cell transplantationBALB/c miceSubset of patientsStem cell transplantationT cell repertoireKey pathologic featuresBALB/cX BALB/Host disease phenotypesCutaneous cGVHDMurine donorsSystemic GVHDC recipientsFrequent complicationCutaneous fibrosisPathologic featuresSystemic diseaseB miceCell transplantationC miceK miceImmunodominant AgDonor APCs are required for maximal GVHD but not for GVL
Matte CC, Liu J, Cormier J, Anderson BE, Athanasiadis I, Jain D, McNiff J, Shlomchik WD. Donor APCs are required for maximal GVHD but not for GVL. Nature Medicine 2004, 10: 987-992. PMID: 15286785, DOI: 10.1038/nm1089.Peer-Reviewed Original ResearchConceptsDonor antigen-presenting cellsAntigen-presenting cellsCD8 cellsMouse modelDonor major histocompatibility complex (MHC) class IBone marrowDonor-derived antigen-presenting cellsChronic phase chronic myelogenous leukemiaHematopoietic antigen-presenting cellsRecipient antigen-presenting cellsHost antigen-presenting cellsMajor histocompatibility complex class IAlloreactive CD8 cellsRecipients of MHCHistocompatibility complex class IDonor-derived cellsMinor histocompatibility antigensChronic myelogenous leukemiaDeficient bone marrowComplex class IHost diseaseGVHDHistocompatibility antigensMyelogenous leukemiaInitial priming
2003
Chronic liver graft-versus-host disease presenting as acute hepatitis
Shinoura S, Jain D, Cooper D, Seropian S, Robert M. Chronic liver graft-versus-host disease presenting as acute hepatitis. The American Journal Of Gastroenterology 2003, 98: s102-s102. DOI: 10.1111/j.1572-0241.2003.08036.x.Peer-Reviewed Original Research