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
2014
Enhanced suppressor function of TIM‐3+FoxP3+ regulatory T cells
Gautron A, Dominguez-Villar M, de Marcken M, Hafler DA. Enhanced suppressor function of TIM‐3+FoxP3+ regulatory T cells. European Journal Of Immunology 2014, 44: 2703-2711. PMID: 24838857, PMCID: PMC4165702, DOI: 10.1002/eji.201344392.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDCell DifferentiationCTLA-4 AntigenFemaleForkhead Transcription FactorsGene Expression RegulationGranzymesHepatitis A Virus Cellular Receptor 2HumansInterleukin 1 Receptor Antagonist ProteinInterleukin-10InterleukinsLymphocyte Activation Gene 3 ProteinMaleMembrane ProteinsMiceMinor Histocompatibility AntigensReceptors, CCR6STAT3 Transcription FactorT-Lymphocytes, RegulatoryTh17 CellsConceptsTim-3 expressionRegulatory T cellsTreg cellsTim-3T cellsNatural regulatory T cellsMucin domain 3Number of TIMTh17 cell responseEffector T cellsT cell suppressionHuman Treg cellsT-cell immunoglobulinAnti-CD28 stimulationT cell differentiationSTAT-3 expressionPathogenic Th1Th17 cellsTc1 cellsImmune toleranceTh1 cellsLevel of expressionReduced gene expressionGene expressionSuppressor function
2009
TIM‐3 is expressed on activated human CD4+ T cells and regulates Th1 and Th17 cytokines
Hastings WD, Anderson DE, Kassam N, Koguchi K, Greenfield EA, Kent SC, Zheng XX, Strom TB, Hafler DA, Kuchroo VK. TIM‐3 is expressed on activated human CD4+ T cells and regulates Th1 and Th17 cytokines. European Journal Of Immunology 2009, 39: 2492-2501. PMID: 19676072, PMCID: PMC2759376, DOI: 10.1002/eji.200939274.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalCD4-Positive T-LymphocytesCytokinesGalectinsHepatitis A Virus Cellular Receptor 2HumansImmunologic FactorsMembrane ProteinsT-Lymphocytes, Helper-InducerTh1 Cells
2008
TIMs: central regulators of immune responses
Hafler DA, Kuchroo V. TIMs: central regulators of immune responses. Journal Of Experimental Medicine 2008, 205: 2699-2701. PMID: 19015312, PMCID: PMC2585854, DOI: 10.1084/jem.20082429.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDApoptosis Regulatory ProteinsHepatitis A Virus Cellular Receptor 2HIV InfectionsHumansImmunityMacaca mulattaMembrane ProteinsMiceProgrammed Cell Death 1 ReceptorReceptors, VirusT-LymphocytesVirus DiseasesConceptsExhausted T cellsT cell exhaustionHIV infectionPD-1T cellsCell exhaustionMucin domain-containing protein 3Chronic HIV infectionChronic viral infectionsHuman HIV infectionT cell responsesChronic viral diseasesT-cell immunoglobulinDomain-containing protein 3Novel therapeutic targetTim-3Opportunistic infectionsCell immunoglobulinImmune responseTherapeutic targetViral infectionCell responsesProtein 3InfectionViral diseasesMultiple Sclerosis and Regulatory T Cells
Costantino CM, Baecher-Allan C, Hafler DA. Multiple Sclerosis and Regulatory T Cells. Journal Of Clinical Immunology 2008, 28: 697-706. PMID: 18763026, PMCID: PMC2752287, DOI: 10.1007/s10875-008-9236-x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutoimmunityCentral Nervous SystemHepatitis A Virus Cellular Receptor 2HumansImmunotherapyMembrane ProteinsMultiple SclerosisT-Lymphocytes, CytotoxicT-Lymphocytes, RegulatoryToll-Like ReceptorsConceptsRegulatory T cellsCentral nervous systemAutoreactive T cellsT cellsAntigen-specific Treg cellsAutoreactive effector T cellsAutoimmune tissue damageFrequency of TregsOrgan-specific autoimmunityEffector T cellsReactive T cellsBlood-brain barrierPathology of MSIntroductionMultiple sclerosisTreg cellsMS patientsPeripheral toleranceChronic inflammationMultiple sclerosisImmune disordersNew therapiesHealthy individualsNervous systemTissue damageDisease modelsLack of TIM-3 Immunoregulation in Multiple Sclerosis
Yang L, Anderson DE, Kuchroo J, Hafler DA. Lack of TIM-3 Immunoregulation in Multiple Sclerosis. The Journal Of Immunology 2008, 180: 4409-4414. PMID: 18354161, DOI: 10.4049/jimmunol.180.7.4409.Peer-Reviewed Original ResearchMeSH KeywordsAdultApoptosisCD4-Positive T-LymphocytesCells, CulturedGene Expression RegulationHepatitis A Virus Cellular Receptor 2HumansInterferon-gammaMembrane ProteinsMultiple SclerosisConceptsMultiple sclerosisT cell functionTim-3Untreated patientsTreatment of MSType 1 Th cellsBlocking Tim-3Tim-3 functionTim-3 regulationT-cell infiltratesTim-3 expressionPeripheral immune systemCell functionHuman autoimmune diseasesIFN-gamma secretionCNS white matterT cell stimulationHuman Tim-3Cell infiltrateGlatiramer acetateImmune toleranceAutoimmune diseasesControl subjectsTh cellsInflammatory diseases
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
2006
Dysregulated T cell expression of TIM3 in multiple sclerosis
Koguchi K, Anderson DE, Yang L, O'Connor KC, Kuchroo VK, Hafler DA. Dysregulated T cell expression of TIM3 in multiple sclerosis. Journal Of Experimental Medicine 2006, 203: 1413-1418. PMID: 16754722, PMCID: PMC2118310, DOI: 10.1084/jem.20060210.Peer-Reviewed Original ResearchMeSH KeywordsClone CellsGene Expression RegulationHepatitis A Virus Cellular Receptor 2HumansLymphocyte ActivationMembrane ProteinsMultiple SclerosisReceptors, VirusT-LymphocytesConceptsIFN-gamma secretionCSF clonesT cell expressionMultiple sclerosisT cellsHuman T cellsTIM3 expressionControl subjectsCerebrospinal fluidCell expressionMucin-domain-containing moleculesPathogenesis of MSEx vivo CD4Human autoimmune diseasesT helper cellsT-cell immunoglobulinT cell clonesVivo CD4Costimulatory blockadeTh1 responseCytokine profileCell surface moleculesAutoimmune diseasesHelper cellsInterleukin-12
2004
T Cell Ig- and Mucin-Domain-Containing Molecule-3 (TIM-3) and TIM-1 Molecules Are Differentially Expressed on Human Th1 and Th2 Cells and in Cerebrospinal Fluid-Derived Mononuclear Cells in Multiple Sclerosis
Khademi M, Illés Z, Gielen AW, Marta M, Takazawa N, Baecher-Allan C, Brundin L, Hannerz J, Martin C, Harris RA, Hafler DA, Kuchroo VK, Olsson T, Piehl F, Wallström E. T Cell Ig- and Mucin-Domain-Containing Molecule-3 (TIM-3) and TIM-1 Molecules Are Differentially Expressed on Human Th1 and Th2 Cells and in Cerebrospinal Fluid-Derived Mononuclear Cells in Multiple Sclerosis. The Journal Of Immunology 2004, 172: 7169-7176. PMID: 15153541, DOI: 10.4049/jimmunol.172.11.7169.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedCell LineCell PolarityCerebrospinal FluidCytokinesFemaleGene Expression RegulationHepatitis A Virus Cellular Receptor 1Hepatitis A Virus Cellular Receptor 2HumansMaleMembrane GlycoproteinsMembrane ProteinsMiddle AgedMultiple SclerosisReceptors, VirusRNA, MessengerTh1 CellsTh2 CellsConceptsCerebrospinal fluid mononuclear cellsFluid mononuclear cellsT cell IgMononuclear cellsTim-3Multiple sclerosisTh2 cellsTIM-1Human Th1TIM moleculesMucin-domain-containing moleculesTim-3 mRNA levelsTh2-mediated diseasesHigh expressionExperimental autoimmune encephalomyelitisHuman autoimmune diseasesTIM-1 expressionIFN-gamma mRNAReal-time RT-PCRTim-1 polymorphismsTh1 cell clonesHigher mRNA expressionAirway hyperreactivityClinical remissionAutoimmune encephalomyelitis