2024
Neutrophils insert elastase into hepatocytes to regulate calcium signaling in alcohol-associated hepatitis
Ogino N, Leite M, Guerra M, Kruglov E, Asashima H, Hafler D, Ito T, Pereira J, Peiffer B, Sun Z, Ehrlich B, Nathanson M. Neutrophils insert elastase into hepatocytes to regulate calcium signaling in alcohol-associated hepatitis. Journal Of Clinical Investigation 2024, 134: e171691. PMID: 38916955, PMCID: PMC11324315, DOI: 10.1172/jci171691.Peer-Reviewed Original ResearchAlcohol-associated hepatitisReduced cell proliferationCalcium channel expressionCalcium signaling mechanismsIntracellular calcium channelsCell proliferationRegulate calcium signalingNeutrophil extracellular trapsChannel expressionNeutrophil granule proteinsCalcium channelsNeutrophil infiltrationPatient specimensGranule proteasesMouse modelHealthy subjectsLiver diseaseExtracellular trapsCalcium signalingSerpin E2NeutrophilsElastase activityHepatitisTissue remodelingSignaling mechanisms
2017
Functional differences between PD-1+ and PD-1- CD4+ effector T cells in healthy donors and patients with glioblastoma multiforme
Goods BA, Hernandez AL, Lowther DE, Lucca LE, Lerner BA, Gunel M, Raddassi K, Coric V, Hafler DA, Love JC. Functional differences between PD-1+ and PD-1- CD4+ effector T cells in healthy donors and patients with glioblastoma multiforme. PLOS ONE 2017, 12: e0181538. PMID: 28880903, PMCID: PMC5589094, DOI: 10.1371/journal.pone.0181538.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsPD-1 expressionEffector T cellsPD-1Effector cellsGlioblastoma multiformeCheckpoint inhibitorsTim-3T cellsHealthy subjectsCell death protein 1Features of exhaustionDeath protein 1T cell compartmentContext of GBMRecovery of functionCD4 effectorsCD4 cellsRNA sequencingTreatment of cancerHealthy donorsGBM patientsBrain cancerCD4Tumors
2016
PD-1 marks dysfunctional regulatory T cells in malignant gliomas
Lowther DE, Goods BA, Lucca LE, Lerner BA, Raddassi K, van Dijk D, Hernandez AL, Duan X, Gunel M, Coric V, Krishnaswamy S, Love JC, Hafler DA. PD-1 marks dysfunctional regulatory T cells in malignant gliomas. JCI Insight 2016, 1: e85935. PMID: 27182555, PMCID: PMC4864991, DOI: 10.1172/jci.insight.85935.Peer-Reviewed Original ResearchTumor-infiltrating TregsPD-1IFN-γ productionGlioblastoma multiformeT cellsImmune responseHealthy subjectsDysfunctional regulatory T cellsHigh PD-1 expressionCell death protein 1PD-1-blocking antibodiesPD-1 expressionEffector T cellsRegulatory T cellsDeath protein 1Antitumoral immune responseImmune checkpoint receptorsProduction of IFNExhausted phenotypeExhaustion signaturesCheckpoint receptorsHuman TregsTumor infiltratesFunctional statusMalignant gliomas
2015
Functional inflammatory profiles distinguish myelin-reactive T cells from patients with multiple sclerosis
Cao Y, Goods BA, Raddassi K, Nepom GT, Kwok WW, Love JC, Hafler DA. Functional inflammatory profiles distinguish myelin-reactive T cells from patients with multiple sclerosis. Science Translational Medicine 2015, 7: 287ra74. PMID: 25972006, PMCID: PMC4497538, DOI: 10.1126/scitranslmed.aaa8038.Peer-Reviewed Original ResearchConceptsMyelin-reactive T cellsMultiple sclerosisT cellsHealthy controlsT cell librariesT helper cell 17Antigen-specific T cellsGene signatureMore IL-10More proinflammatory cytokinesAutoreactive T cellsIL-10 productionHuman autoimmune diseasesGranulocyte-macrophage colony-stimulating factorProduction of interferonColony-stimulating factorMyelin antigensTh17 cellsIL-10Inflammatory profileInterleukin-17Proinflammatory cytokinesAutoimmune diseasesDisease progressionHealthy subjects
2014
Decreased RORC-dependent silencing of prostaglandin receptor EP2 induces autoimmune Th17 cells
Kofler DM, Marson A, Dominguez-Villar M, Xiao S, Kuchroo VK, Hafler DA. Decreased RORC-dependent silencing of prostaglandin receptor EP2 induces autoimmune Th17 cells. Journal Of Clinical Investigation 2014, 124: 2513-2522. PMID: 24812667, PMCID: PMC4089462, DOI: 10.1172/jci72973.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsAutoimmunityCase-Control StudiesDinoprostoneDown-RegulationFemaleGene Knockdown TechniquesGene SilencingHumansMaleMiceMice, Inbred C57BLMice, KnockoutMiddle AgedModels, ImmunologicalMultiple SclerosisNuclear Receptor Subfamily 1, Group F, Member 3PhenotypePromoter Regions, GeneticReceptors, Prostaglandin E, EP2 SubtypeSignal TransductionTh17 CellsConceptsTh17 cell phenotypeProstaglandin receptor EP2Receptor EP2Healthy individualsOverexpression of EP2Transcription factor RORCT cell subsetsEffects of PGE2Cell phenotypeExpression of IFNInflammatory gene transcriptionPGE2-dependent pathwayTh17 cellsWT miceAutoimmune diseasesCell subsetsHealthy subjectsEP2 expressionGM-CSFEP2RORCCD4Cell typesCellsGene transcription
2007
Multispecific responses by T cells expanded by endogenous self‐peptide/MHC complexes
Cai G, Hafler DA. Multispecific responses by T cells expanded by endogenous self‐peptide/MHC complexes. European Journal Of Immunology 2007, 37: 602-612. PMID: 17304631, DOI: 10.1002/eji.200636787.Peer-Reviewed Original ResearchConceptsT cellsHuman T cell responsesSelf-peptide/MHCSelf-peptide/MHC complexesEndogenous self-antigenPercentage of CD4Pathological immune responsesT cell responsesAntigen-presenting cellsT cell clonesCell cycleMultispecific responseMHC determinantsSelf antigensAntigen stimulationHealthy subjectsImmune responseAntigen reactivityCD4Cell responsesMultiple antigensCD28 costimulationMHC complexesCell clonesTCRbeta chain
2006
Alterations in CD46-mediated Tr1 regulatory T cells in patients with multiple sclerosis
Astier AL, Meiffren G, Freeman S, Hafler DA. Alterations in CD46-mediated Tr1 regulatory T cells in patients with multiple sclerosis. Journal Of Clinical Investigation 2006, 116: 3252-3257. PMID: 17099776, PMCID: PMC1635165, DOI: 10.1172/jci29251.Peer-Reviewed Original ResearchConceptsIL-10 secretionTr1 regulatory T cellsRegulatory T cellsHuman autoimmune diseasesMultiple sclerosisT cellsAutoimmune diseasesTr1 cellsIL-10Antiinflammatory cytokine IL-10Cytokine IL-10IFN-gamma secretionT cell functionT cell activationHuman T cellsTreg defectsTreg phenotypeTreg functionCostimulatory moleculesHealthy subjectsMurine modelCD46 costimulationCell activationCD28 costimulationPatients
2004
Regulatory T cells in type 1 diabetes mellitus
Viglietta V, Baecher-Allan C, Hafler A, Gottlieb P. Regulatory T cells in type 1 diabetes mellitus. Current Opinion In Endocrinology Diabetes And Obesity 2004, 11: 85-90. DOI: 10.1097/01.med.0000129641.34639.2e.Peer-Reviewed Original ResearchRegulatory T cellsType 1 diabetes mellitusType 1 diabetesT cellsDiabetes mellitusT lymphocytesHuman type 1 diabetesΒ-cell antigensNK T cellsTh2-type responseMost healthy subjectsReactive T lymphocytesOnset of diseaseInsulin-producing β-cellsAutoimmune conditionsPeripheral toleranceRegulatory cellsPeripheral deletionSpecific immunizationTh2 cytokinesAutoimmune diseasesHealthy subjectsAntigen reactivityHealthy individualsAnergy induction
2000
Glatiramer acetate (Copaxone®) induces degenerate, Th2-polarized immune responses in patients with multiple sclerosis
Duda PW, Schmied MC, Cook SL, Krieger JI, Hafler DA. Glatiramer acetate (Copaxone®) induces degenerate, Th2-polarized immune responses in patients with multiple sclerosis. Journal Of Clinical Investigation 2000, 105: 967-976. PMID: 10749576, PMCID: PMC377485, DOI: 10.1172/jci8970.Peer-Reviewed Original ResearchMeSH KeywordsAdultAmino Acid SequenceCell DivisionCells, CulturedCross ReactionsEpitopes, T-LymphocyteFemaleGlatiramer AcetateHumansImmunodominant EpitopesImmunosuppressive AgentsInterferon-gammaInterleukin-5Leukocytes, MononuclearLigandsMaleMiddle AgedMolecular Sequence DataMultiple SclerosisMyelin Basic ProteinMyelin SheathPeptide FragmentsPeptidesTetanus ToxoidTh2 CellsConceptsT cell responsesMultiple sclerosisGlatiramer acetateT cellsAntigen-specific T cell responsesTh2-polarized immune responseCross-reactive T cellsAlters immune functionHuman autoimmune diseasesAcetate inducesCross-reactive responsesT cell receptorT cell linesImmune deviationMost patientsTh2 typeAutoimmune disordersTh2 cytokinesAutoimmune diseasesDaily injectionsIL-13IL-5Th2 cellsHealthy subjectsImmune response
1999
T cell Autoreactivity to Proinsulin Epitopes in Diabetic Patients and Healthy Subjects
Semana G, Gausling R, Jackson R, Hafler D. T cell Autoreactivity to Proinsulin Epitopes in Diabetic Patients and Healthy Subjects. Journal Of Autoimmunity 1999, 12: 259-267. PMID: 10330297, DOI: 10.1006/jaut.1999.0282.Peer-Reviewed Original ResearchConceptsProinsulin epitopesImmune responseProliferative responseReactive cellsPeptide-specific T cellsShort-term cell linesSpecific T cell clonesHigher 3H-thymidine incorporationPredominant immune responseT cell autoreactivitySpecific T cellsLow proliferative responseTissue-specific autoantigensT cell clonesCD3-CD28IDDM groupIDDM patientsDiabetic patientsControl subjectsDisease onsetPotential autoantigensStrong TCR signalsC-peptideT cellsHealthy subjects
1990
Shared Human T Cell Receptor Vβ Usage to Immunodominant Regions of Myelin Basic Protein
Wucherpfennig K, Ota K, Endo N, Seidman JG, Rosenzweig A, Weiner H, Hafler D. Shared Human T Cell Receptor Vβ Usage to Immunodominant Regions of Myelin Basic Protein. Science 1990, 248: 1016-1019. PMID: 1693015, DOI: 10.1126/science.1693015.Peer-Reviewed Original ResearchConceptsMultiple sclerosisImmunodominant regionMyelin basic proteinMS patientsT cellsBeta 17T cell receptor Vβ usageTCR V beta gene usageReactive T cellsBeta gene usageT cell receptor beta chainT cell linesBasic proteinSpecific immunotherapyVβ usageAutoimmune diseasesReceptor beta chainHealthy subjectsTarget antigenGene usageBeta 12Myelin proteinsTCR structureHuman MBPBeta chain