2022
Impaired TIGIT expression on B cells drives circulating follicular helper T cell expansion in multiple sclerosis
Asashima H, Axisa PP, Pham THG, Longbrake EE, Ruff WE, Lele N, Cohen I, Raddassi K, Sumida TS, Hafler DA. Impaired TIGIT expression on B cells drives circulating follicular helper T cell expansion in multiple sclerosis. Journal Of Clinical Investigation 2022, 132: e156254. PMID: 36250467, PMCID: PMC9566906, DOI: 10.1172/jci156254.Peer-Reviewed Original ResearchConceptsRelapsing-remitting multiple sclerosisMemory B cellsCTfh cellsB cellsTIGIT expressionMultiple sclerosisT cellsFollicular helper T cellsHealthy age-matched controlsB-cell depletionT cell expansionHelper T cellsAge-matched controlsB cell functionB-cell pathwayDifferential gene expression signaturesTfh cellsDisease activityGene expression signaturesCell depletionCD40 ligandTranscription factor TCF4Disease pathogenesisImmune systemNew MRIType I interferon transcriptional network regulates expression of coinhibitory receptors in human T cells
Sumida TS, Dulberg S, Schupp JC, Lincoln MR, Stillwell HA, Axisa PP, Comi M, Unterman A, Kaminski N, Madi A, Kuchroo VK, Hafler DA. Type I interferon transcriptional network regulates expression of coinhibitory receptors in human T cells. Nature Immunology 2022, 23: 632-642. PMID: 35301508, PMCID: PMC8989655, DOI: 10.1038/s41590-022-01152-y.Peer-Reviewed Original ResearchMeSH KeywordsCOVID-19Gene Regulatory NetworksHumansInterferon Type IReceptors, Antigen, T-CellReceptors, ImmunologicSARS-CoV-2T-LymphocytesConceptsCoinhibitory receptor expressionHuman T cellsIFN-I responsesCoinhibitory receptorsT cellsTIGIT expressionReceptor expressionAcute SARS-CoV-2 infectionPD-1/TimSARS-CoV-2 infectionEnhancement of immunotherapyType 1 interferonT-cell featuresLAG-3Infectious diseasesDifferent temporal kineticsTranscription factorsCancer therapyReceptorsCell featuresKey transcription factorIFNPresent studyMRNA profilingKey regulator
2020
Differential expression of the T-cell inhibitor TIGIT in glioblastoma and MS
Lucca LE, Lerner BA, Park C, DeBartolo D, Harnett B, Kumar VP, Ponath G, Raddassi K, Huttner A, Hafler DA, Pitt D. Differential expression of the T-cell inhibitor TIGIT in glioblastoma and MS. Neurology Neuroimmunology & Neuroinflammation 2020, 7: e712. PMID: 32269065, PMCID: PMC7188477, DOI: 10.1212/nxi.0000000000000712.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedCentral Nervous System NeoplasmsFemaleGlioblastomaHumansMaleMiddle AgedMultiple SclerosisReceptors, ImmunologicUp-RegulationConceptsTumor-infiltrating T cellsT cellsPD-1/PD-L1Anti-TIGIT therapyExpression of CD226Expression of TIGITPostmortem CNS tissueLymphocytes of patientsFresh surgical resectionsLigand CD155TIGIT expressionSurgical resectionPD-1PD-L1CNS diseaseHealthy controlsHealthy donorsLymphocytic expressionImmune responseCNS tissueMS lesionsTIGITImmune pathwaysPatientsGlioblastoma multiforme
2014
Treg Cells Expressing the Coinhibitory Molecule TIGIT Selectively Inhibit Proinflammatory Th1 and Th17 Cell Responses
Joller N, Lozano E, Burkett PR, Patel B, Xiao S, Zhu C, Xia J, Tan TG, Sefik E, Yajnik V, Sharpe AH, Quintana FJ, Mathis D, Benoist C, Hafler DA, Kuchroo VK. Treg Cells Expressing the Coinhibitory Molecule TIGIT Selectively Inhibit Proinflammatory Th1 and Th17 Cell Responses. Immunity 2014, 40: 569-581. PMID: 24745333, PMCID: PMC4070748, DOI: 10.1016/j.immuni.2014.02.012.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell ProliferationCells, CulturedCytokinesEosinophilsFibrinogenForkhead Transcription FactorsGene Expression ProfilingGene Expression RegulationImmunosuppression TherapyLymphocyte ActivationMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicReceptors, ImmunologicRespiratory HypersensitivityT-Lymphocyte SubsetsT-Lymphocytes, RegulatoryTh1-Th2 BalanceConceptsTreg cell subsetsTh2 cell responsesTreg cellsCell subsetsCell responsesProinflammatory T helper 1T effector cell proliferationTreg cell-mediated suppressionFibrinogen-like protein 2Allergic airway inflammationT regulatory (Treg) cellsTh2 cytokine productionSuppression of Th1T helper 1Effector cell proliferationTreg signature genesProinflammatory Th1TIGIT expressionAirway inflammationTh17 cellsRegulatory cellsHelper 1Cytokine productionT cellsImmune responsepRESTO: a toolkit for processing high-throughput sequencing raw reads of lymphocyte receptor repertoires
Vander Heiden JA, Yaari G, Uduman M, Stern JN, O'Connor KC, Hafler DA, Vigneault F, Kleinstein SH. pRESTO: a toolkit for processing high-throughput sequencing raw reads of lymphocyte receptor repertoires. Bioinformatics 2014, 30: 1930-1932. PMID: 24618469, PMCID: PMC4071206, DOI: 10.1093/bioinformatics/btu138.Peer-Reviewed Original Research
2012
The TIGIT/CD226 Axis Regulates Human T Cell Function
Lozano E, Dominguez-Villar M, Kuchroo V, Hafler DA. The TIGIT/CD226 Axis Regulates Human T Cell Function. The Journal Of Immunology 2012, 188: 3869-3875. PMID: 22427644, PMCID: PMC3324669, DOI: 10.4049/jimmunol.1103627.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntigens, Differentiation, T-LymphocyteCD4-Positive T-LymphocytesCell CommunicationCell ProliferationCells, CulturedCytokinesDendritic CellsGATA3 Transcription FactorGene Expression RegulationHumansImmune ToleranceReceptors, ImmunologicReceptors, VirusRNA, Small InterferingSignal TransductionT-Box Domain ProteinsConceptsT cell functionT cellsAutoimmune diseasesT-betTIGIT/CD226 axisHuman T cell responsesT cell-intrinsic mannerHuman T cell functionAlternative costimulatory pathwaysT cell responsesCell functionDendritic cell surfaceHuman autoimmune diseasesIL-10 expressionT cell IgIFN regulatory factor 4T cell proliferationOrphan receptor CDirect inhibitory effectIFN-γ mRNACell-intrinsic mannerRegulatory factor 4TIGIT expressionTIGIT knockdownTolerogenic phenotype
2007
Promotion of Tissue Inflammation by the Immune Receptor Tim-3 Expressed on Innate Immune Cells
Anderson AC, Anderson DE, Bregoli L, Hastings WD, Kassam N, Lei C, Chandwaskar R, Karman J, Su EW, Hirashima M, Bruce JN, Kane LP, Kuchroo VK, Hafler DA. Promotion of Tissue Inflammation by the Immune Receptor Tim-3 Expressed on Innate Immune Cells. Science 2007, 318: 1141-1143. PMID: 18006747, DOI: 10.1126/science.1148536.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAstrocytesCD11b AntigenCentral Nervous System NeoplasmsDendritic CellsEncephalomyelitis, Autoimmune, ExperimentalGalectinsGlioblastomaHepatitis A Virus Cellular Receptor 2HumansImmunity, InnateInflammation MediatorsLipopolysaccharidesMacrophagesMembrane ProteinsMiceMicrogliaMultiple SclerosisRatsReceptors, ImmunologicReceptors, VirusSignal TransductionT-LymphocytesTh1 CellsToll-Like ReceptorsConceptsImmune receptor Tim-3Tim-3Immune cellsT helper 1 cellsAdaptive immune cellsInnate immune cellsToll-like receptorsInduced Immune ResponsesInnate immune systemTh1 immunityDendritic cellsTissue inflammationInflammatory conditionsT cellsImmune responseImmune systemImportant mediatorAntibody agonistsInflammationCell typesLatter findingNumerous pathwaysCellsDifferential expressionCD4
1998
Natural killer activating receptors trigger interferon γ secretion from T cells and natural killer cells
Mandelboim O, Kent S, Davis D, Wilson S, Okazaki T, Jackson R, Hafler D, Strominger J. Natural killer activating receptors trigger interferon γ secretion from T cells and natural killer cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 1998, 95: 3798-3803. PMID: 9520447, PMCID: PMC19917, DOI: 10.1073/pnas.95.7.3798.Peer-Reviewed Original ResearchMeSH KeywordsCD56 AntigenHistocompatibility Antigens Class IHumansInterferon-gammaKiller Cells, NaturalLymphocyte ActivationReceptors, ImmunologicT-LymphocytesConceptsNatural killer cell activating receptorsT cellsNK cellsInterferon γ secretionSubset of CD8Target cellsHuman class I major histocompatibility complex (MHC) moleculesNatural killer cellsInterferon-gamma secretionGammadelta T cellsMajor histocompatibility complex moleculesAlphabeta T cellsClass I MHC moleculesClass I major histocompatibility complex moleculesTypes of lymphocytesMHC class IHistocompatibility complex moleculesI MHC moleculesT cell receptorEnhancement of proliferationΓ secretionGamma secretionNatural killerKiller cellsActivating receptors
1992
T cell receptor V alpha-V beta repertoire and cytokine gene expression in active multiple sclerosis lesions.
Wucherpfennig KW, Newcombe J, Li H, Keddy C, Cuzner ML, Hafler DA. T cell receptor V alpha-V beta repertoire and cytokine gene expression in active multiple sclerosis lesions. Journal Of Experimental Medicine 1992, 175: 993-1002. PMID: 1348083, PMCID: PMC2119186, DOI: 10.1084/jem.175.4.993.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAntigens, Differentiation, T-LymphocyteBase SequenceCD2 AntigensChronic DiseaseClone CellsCytokinesGene ExpressionHumansInterleukin-1Interleukin-2Interleukin-4Molecular Sequence DataMultiple SclerosisOligodeoxyribonucleotidesPolymerase Chain ReactionReceptors, Antigen, T-Cell, alpha-betaReceptors, ImmunologicRNA, MessengerConceptsTCR V alphaTCR repertoireBeta repertoireMultiple sclerosisV alphaActive lesionsMS plaquesT cellsAlpha/beta T cellsActive multiple sclerosis lesionsMS plaque tissueCentral nervous system tissueT cell recruitmentBeta T cellsActive MS plaquesChronic inflammatory diseaseIL-4 mRNAT cell expansionIL-1 mRNATCR V gene segmentsCentral nervous systemCases of subacuteNervous system tissueSites of inflammationTCR V genes
1991
Presentation of autoantigen by human T cells.
LaSalle JM, Ota K, Hafler DA. Presentation of autoantigen by human T cells. The Journal Of Immunology 1991, 147: 774-80. PMID: 1713605, DOI: 10.4049/jimmunol.147.3.774.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAntigens, CDAntigens, Differentiation, T-LymphocyteAntigens, SurfaceAutoantigensCD2 AntigensCD58 AntigensEpitopesHistocompatibility AntigensHLA-D AntigensHumansIntegrin beta1Leukocyte Common AntigensLymphocyte ActivationLymphocyte Function-Associated Antigen-1Membrane GlycoproteinsMolecular Sequence DataMyelin Basic ProteinReceptors, ImmunologicT-LymphocytesConceptsT cell clonesMBP-reactive T cell clonesAutologous T cellsMyelin basic proteinMHC class IIT cellsHuman T cellsCell clonesAdhesion molecules LFA-3Class IIReactive T cell clonesWhole myelin basic proteinPresentation of autoantigensT cell interactionsActivated T cellsT cell presentationTCR-mediated responsesAg preparationsImmune responseMHC classSelf-AgForeign AgsInflammatory sitesCell presentationLFA-3
1989
Inflammatory cerebrospinal fluid t cells have activation requirements characteristic of cd4+cd45ra‐ t cells
Chofflon M, González V, Weiner H, Hafler D. Inflammatory cerebrospinal fluid t cells have activation requirements characteristic of cd4+cd45ra‐ t cells. European Journal Of Immunology 1989, 19: 1791-1795. PMID: 2479560, DOI: 10.1002/eji.1830191005.Peer-Reviewed Original ResearchConceptsCSF T cellsPhorbol myristate acetateMononuclear cellsCSF mononuclear cellsT cellsCerebrospinal fluidCerebrospinal fluid T cellsCSF of subjectsProtein kinase CCD3/T cell receptor complexInflammatory brain diseasesBlood mononuclear cellsT cell populationsSorted T cellsInterleukin-2 receptorInterleukin-2 secretionCD2 activation pathwayT cell receptor complexKinase CInflammatory compartmentMultiple sclerosisCNS diseaseCell receptor complexImmune responseNormal subjectsMechanisms of immune memory. T cell activation and CD3 phosphorylation correlates with Ta1 (CDw26) expression.
Hafler DA, Chofflon M, Benjamin D, Dang NH, Breitmeyer J. Mechanisms of immune memory. T cell activation and CD3 phosphorylation correlates with Ta1 (CDw26) expression. The Journal Of Immunology 1989, 142: 2590-6. PMID: 2564857, DOI: 10.4049/jimmunol.142.8.2590.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, Differentiation, T-LymphocyteAntigens, SurfaceCalciumCD2 AntigensCD3 ComplexHumansImmunologic MemoryLymphocyte ActivationPhosphorylationProtein Kinase CReceptors, Antigen, T-CellReceptors, ImmunologicT-LymphocytesTetradecanoylphorbol AcetateTumor Necrosis Factor Receptor Superfamily, Member 7ConceptsT cell immune memoryT cell activationImmune memoryT cellsCell activationPeripheral blood T cellsTA1 expressionBlood T cellsIntracellular calcium levelsTA1 cellsCD3/TCRT cell linesCalcium ionophore ionomycinAg challengeIL-2T lymphocytesMitogenic antibodiesCalcium levelsPhorbol ester PMAIonophore ionomycinCD2 moleculeGrowth factorActivation requirementsInvariant chainCD2 stimulation
1988
Anti‐CD4 and Anti‐CD2 Monoclonal Antibody Infusions in Subjects with Multiple Sclerosis Immunosuppressive Effects and Human Antimouse Responses
HAFLER D, WEINER H. Anti‐CD4 and Anti‐CD2 Monoclonal Antibody Infusions in Subjects with Multiple Sclerosis Immunosuppressive Effects and Human Antimouse Responses. Annals Of The New York Academy Of Sciences 1988, 540: 557-559. PMID: 2905125, DOI: 10.1111/j.1749-6632.1988.tb27171.x.Peer-Reviewed Original Research
1985
Investigation of in vivo activated T cells in multiple sclerosis and inflammatory central nervous system diseases
Hafler DA, Hemler ME, Christenson L, Williams JM, Shapiro HM, Strom TB, Strominger JL, Weiner HL. Investigation of in vivo activated T cells in multiple sclerosis and inflammatory central nervous system diseases. Clinical Immunology 1985, 37: 163-171. PMID: 3930113, DOI: 10.1016/0090-1229(85)90147-3.Peer-Reviewed Original ResearchConceptsT cellsActivated T cellsActivation antigensMultiple sclerosisInflammatory central nervous system diseasesPeripheral blood T cellsCentral nervous system diseaseActive multiple sclerosisSystemic immune activationGroup of patientsMultiple sclerosis patientsBlood T cellsEarly activation antigenNervous system diseasesAbnormal immunologic activityMultiple differentiation stagesMS patientsSclerosis patientsViral encephalitisImmune activationPeripheral bloodNeurologic diseaseImmunologic activitySystem diseasesNormal controls