2016
The Link Between CD6 and Autoimmunity: Genetic and Cellular Associations.
Kofler DM, Farkas A, von Bergwelt-Baildon M, Hafler DA. The Link Between CD6 and Autoimmunity: Genetic and Cellular Associations. Current Drug Targets 2016, 17: 651-65. PMID: 26844569, DOI: 10.2174/1389450117666160201105934.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDAntigens, Differentiation, T-LymphocyteArthritis, RheumatoidAutoimmunityCD4-Positive T-LymphocytesCell Adhesion Molecules, NeuronalClinical Trials as TopicDisease Models, AnimalFetal ProteinsGenetic Predisposition to DiseaseHumansMultiple SclerosisPolymorphism, Single NucleotideConceptsMultiple sclerosisRheumatoid arthritisCentral nervous systemNervous systemSingle nucleotide polymorphismsDevelopment of MSTreatment of RARole of CD6T cell traffickingT cell functionGenetic risk factorsEndothelial cell barrierCD6 geneClinical responseGenetic associationClinical featuresAutoimmune diseasesSynovial cellsRisk factorsTumor necrosisSynovial fibroblastsPossible common mechanismT cellsT lymphocytesLeukocyte trafficking
2013
The CD226/CD155 Interaction Regulates the Proinflammatory (Th1/Th17)/Anti-Inflammatory (Th2) Balance in Humans
Lozano E, Joller N, Cao Y, Kuchroo VK, Hafler DA. The CD226/CD155 Interaction Regulates the Proinflammatory (Th1/Th17)/Anti-Inflammatory (Th2) Balance in Humans. The Journal Of Immunology 2013, 191: 3673-3680. PMID: 23980210, PMCID: PMC3819731, DOI: 10.4049/jimmunol.1300945.Peer-Reviewed Original ResearchConceptsNaive T cellsT cellsInflammatory balanceIL-13IL-17-producing cellsRole of CD226IL-17 productionIL-17 secretionHuman autoimmune diseasesIFN-γ productionIL-13 secretionIFN-γ expressionProduction of IFNSTAT-6 phosphorylationT cell activationHuman T cellsLigand CD155Th17 cellsIL-17Autoimmune diseasesIL-4T-betTh1 differentiationTh17 conditionsTherapeutic approaches
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
2011
The CD6 Multiple Sclerosis Susceptibility Allele Is Associated with Alterations in CD4+ T Cell Proliferation
Kofler DM, Severson CA, Mousissian N, De Jager PL, Hafler DA. The CD6 Multiple Sclerosis Susceptibility Allele Is Associated with Alterations in CD4+ T Cell Proliferation. The Journal Of Immunology 2011, 187: 3286-3291. PMID: 21849685, DOI: 10.4049/jimmunol.1100626.Peer-Reviewed Original ResearchMeSH KeywordsAllelesAntigens, CDAntigens, Differentiation, T-LymphocyteCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell ProliferationCell SeparationCells, CulturedFemaleFlow CytometryGenetic Predisposition to DiseaseGenotypeHumansMaleMultiple SclerosisPhenotypeReverse Transcriptase Polymerase Chain ReactionRisk FactorsRNA, Small InterferingConceptsGenome-wide association studiesAssociation studiesAllelic variantsNew susceptibility lociSusceptibility allelesRisk allelesProliferation defectExon 5Risk-associated allelesSingle nucleotide polymorphismsExtracellular binding sitesCD6 geneSusceptibility lociLinkage disequilibriumMS risk alleleSelective knockdownT cell activationNucleotide polymorphismsAltered proliferationCell proliferationGenetic associationAllelesLong-term activationBinding sitesMS susceptibility alleles
2009
Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci
De Jager PL, Jia X, Wang J, de Bakker PI, Ottoboni L, Aggarwal NT, Piccio L, Raychaudhuri S, Tran D, Aubin C, Briskin R, Romano S, Baranzini S, McCauley J, Pericak-Vance M, Haines J, Gibson R, Naeglin Y, Uitdehaag B, Matthews P, Kappos L, Polman C, McArdle W, Strachan D, Evans D, Cross A, Daly M, Compston A, Sawcer S, Weiner H, Hauser S, Hafler D, Oksenberg J. Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci. Nature Genetics 2009, 41: 776-782. PMID: 19525953, PMCID: PMC2757648, DOI: 10.1038/ng.401.Peer-Reviewed Original Research
2002
Strength of prior stimuli determines the magnitude of secondary responsiveness in CD8+ T cells
Lim DG, Höllsberg P, Hafler DA. Strength of prior stimuli determines the magnitude of secondary responsiveness in CD8+ T cells. Cellular Immunology 2002, 217: 36-46. PMID: 12425999, DOI: 10.1016/s0008-8749(02)00511-7.Peer-Reviewed Original ResearchConceptsT cellsSecondary responsivenessCostimulatory moleculesInduction of CD8Magnitude of CD8T cell responsesT cell anergyCell anergyCD8Prior stimulusSecondary stimulationPrimary stimulationCell responsesCellular mechanismsFollowing activationPeptide ligandsActivation thresholdStimulationCellsResponsivenessHigh levelsCD4AnergyStimuliStrength of signal
1993
Increased Protein Kinase C Activity in Human Memory T Cells
Höllsberg P, Melinek J, Benjamin D, Hafler D. Increased Protein Kinase C Activity in Human Memory T Cells. Cellular Immunology 1993, 149: 170-179. PMID: 8099849, DOI: 10.1006/cimm.1993.1145.Peer-Reviewed Original ResearchMeSH KeywordsAlkaloidsAntigens, Differentiation, T-LymphocyteClone CellsDipeptidyl Peptidase 4HumansImmunologic MemoryLymphocyte ActivationPhytohemagglutininsProtein Kinase CReceptors, Interleukin-2StaurosporineT-Lymphocyte SubsetsTetradecanoylphorbol AcetateConceptsCD26 T cellsMemory T cellsT cell populationsMemory T cell populationsT cellsT cell receptorProliferative responseCell populationsPeripheral blood T cellsHuman memory T cellsMemory T cell functionCD26 antigen expressionT-cell surface antigensPKC activityBlood T cellsT cell functionTCR/CD3 pathwayDifferentiated T cellsCell surface antigensCD26 mAbCD26- subsetAntigen challengeAntigen expressionCD26 antigenCD26 expressionDouble-Blind Pilot Trial of Oral Tolerization with Myelin Antigens in Multiple Sclerosis
Weiner H, Mackin G, Matsui M, Orav E, Khoury S, Dawson D, Hafler D. Double-Blind Pilot Trial of Oral Tolerization with Myelin Antigens in Multiple Sclerosis. Science 1993, 259: 1321-1324. PMID: 7680493, DOI: 10.1126/science.7680493.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntigens, Differentiation, T-LymphocyteAutoantigensDouble-Blind MethodFemaleHaplotypesHLA-DR2 AntigenHumansImmune ToleranceMaleMultiple SclerosisMyelin Basic ProteinMyelin SheathPilot ProjectsT-LymphocytesConceptsMultiple sclerosisOral tolerizationMyelin antigensAutoimmune diseasesDouble-blind pilot trialRelapsing-remitting multiple sclerosisDouble-blind studyCentral nervous systemMyelin basic proteinMajor exacerbationsDaily capsuleT cellsT lymphocytesPilot trialSide effectsNervous systemControl groupMyelin componentsBovine myelinDiseaseMyelinTolerizationSclerosisAntigenBasic protein
1992
CTLA-4 and CD28 mRNA are coexpressed in most T cells after activation. Expression of CTLA-4 and CD28 mRNA does not correlate with the pattern of lymphokine production.
Freeman GJ, Lombard DB, Gimmi CD, Brod SA, Lee K, Laning JC, Hafler DA, Dorf ME, Gray GS, Reiser H. CTLA-4 and CD28 mRNA are coexpressed in most T cells after activation. Expression of CTLA-4 and CD28 mRNA does not correlate with the pattern of lymphokine production. The Journal Of Immunology 1992, 149: 3795-801. PMID: 1281186, DOI: 10.4049/jimmunol.149.12.3795.Peer-Reviewed Original ResearchMeSH KeywordsAbataceptAnimalsAntigens, CDAntigens, DifferentiationAntigens, Differentiation, T-LymphocyteAntigens, SurfaceB7-1 AntigenBase SequenceBlotting, NorthernCD28 AntigensCell Adhesion MoleculesCell LineCTLA-4 AntigenHumansImmunoconjugatesInterferon-gammaInterleukinsLeukemia, T-CellLymphocyte ActivationLymphokinesMiceMolecular Sequence DataOligonucleotide ProbesPolymerase Chain ReactionRNA, MessengerT-LymphocytesTumor Necrosis Factor-alphaConceptsT cell clonesCTLA-4 mRNACTLA-4T cellsActivated T cellsT cell activationT cell linesMurine T cell clonesCell clonesCD28 mRNACostimulatory signalsT cell receptor-dependent stimulationCell activationNormal T cell subsetsAg-presenting cellsHuman T cell clonesT cell subsetsExpression of CD28Th2 cytokine profileMost T cellsLeukemic T cell lineCell linesReceptor-dependent stimulationSuch costimulatory signalsInteraction of B7Early signaling defects in human T cells anergized by T cell presentation of autoantigen.
LaSalle JM, Tolentino PJ, Freeman GJ, Nadler LM, Hafler DA. Early signaling defects in human T cells anergized by T cell presentation of autoantigen. Journal Of Experimental Medicine 1992, 176: 177-186. PMID: 1535366, PMCID: PMC2119294, DOI: 10.1084/jem.176.1.177.Peer-Reviewed Original ResearchMeSH KeywordsAntigen-Presenting CellsAntigens, Differentiation, T-LymphocyteAutoantigensCalciumCD3 ComplexCytokinesHLA-DR AntigensHumansImmune ToleranceReceptors, Antigen, T-CellT-LymphocytesTetradecanoylphorbol AcetateConceptsAntigen-presenting cellsT cell presentationPhorbol myristate acetateT cellsAnergized T cellsCell presentationL cell transfectantsProliferative responseAlpha CD3B cellsMajor histocompatibility complex classHuman T cell clonesPrimary proliferative responsesAllogeneic B cellsT cell anergyT cell clonesHistocompatibility complex classInduction of anergyInterferon-gamma mRNANormal proliferative responseT cell activationCD2 monoclonal antibodiesT cell receptorCell transfectantsPresence of costimulationCharacterization of HTLV-I in vivo infected T cell clones. IL-2-independent growth of nontransformed T cells.
Höllsberg P, Wucherpfennig KW, Ausubel LJ, Calvo V, Bierer BE, Hafler DA. Characterization of HTLV-I in vivo infected T cell clones. IL-2-independent growth of nontransformed T cells. The Journal Of Immunology 1992, 148: 3256-63. PMID: 1374452, DOI: 10.4049/jimmunol.148.10.3256.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntigens, Differentiation, T-LymphocyteBase SequenceCD3 ComplexClone CellsCyclosporineHTLV-I InfectionsHumansInterleukin-2Lymphocyte ActivationMolecular Sequence DataPolyenesReceptors, Antigen, T-CellReceptors, Interleukin-2RNA, MessengerSirolimusT-LymphocytesTacrolimusConceptsT cell clonesClonal proliferationCell clonesIL-2 receptor signalLymphotrophic virus type ICharacterization of HTLVInfected T cell clonesHTLV-I provirusBlood of subjectsVirus type IT cell activationAbsence of mitogensIL-2-mediated signalingIL-2-independent growthSite of actionMononuclear cellsIL-2Polymerase chain reactionT cellsExogenous growth factorsPeriodic restimulationFK-506Cell activationHTLVP55 chainT 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-3Immunologic effects of cyclophosphamide/ACTH in patients with chronic progressive multiple sclerosis
Hafler D, Orav J, Gertz R, Stazzone L, Weiner H. Immunologic effects of cyclophosphamide/ACTH in patients with chronic progressive multiple sclerosis. Journal Of Neuroimmunology 1991, 32: 149-158. PMID: 1672870, DOI: 10.1016/0165-5728(91)90007-t.Peer-Reviewed Original ResearchMeSH KeywordsAdrenocorticotropic HormoneAntigens, Differentiation, T-LymphocyteCD3 ComplexCD4-Positive T-LymphocytesCyclophosphamideDipeptidyl Peptidase 4HumansLeukocyte CountMultiple SclerosisReceptors, Antigen, T-CellT-Lymphocytes, RegulatoryConceptsT cell populationsDisability Status ScaleMixed lymphocyte reactionSpontaneous proliferationT cellsImmune measuresACTH infusionImmune functionChronic progressive multiple sclerosisProgressive multiple sclerosis patientsCD4/CD8 ratioCell populationsAllogeneic mixed lymphocyte reactionFunctional immune measuresPeripheral blood CD4Progressive multiple sclerosisPositive clinical responsePositive T cellsMultiple sclerosis patientsFunctional immune assaysLevels of proliferationBlood CD4CD8 ratioClinical improvementClinical response
1990
T‐T cell interactions are mediated by adhesion molecules
Brod S, Purvee M, Benjamin D, Hafler D. T‐T cell interactions are mediated by adhesion molecules. European Journal Of Immunology 1990, 20: 2259-2268. PMID: 1700751, DOI: 10.1002/eji.1830201015.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntigens, Differentiation, T-LymphocyteAntigens, SurfaceCD3 ComplexCD58 AntigensCell Adhesion MoleculesCell CommunicationClone CellsHumansImmunophenotypingInterleukin-2Lymphocyte ActivationLymphocyte Function-Associated Antigen-1Membrane GlycoproteinsMitogensReceptors, Antigen, T-CellT-LymphocytesConceptsT cell clonesAutologous T cell clonesPeripheral blood T cellsAdhesion molecules LFA-1Blood T cellsT cellsLFA-3Major histocompatibility complexInflammatory responseCell clonesICAM-1LFA-1T cell immune functionCD3/T cell receptor complexSpecific T cellsCell adhesion molecules LFA-1Cell immune functionT cell interactionsT cell activationT cell receptor complexMHC determinantsCell receptor complexImmune functionCell activationCD2 pathwayFrequency analysis of CD4+CD8+ T cells cloned with IL-4
Brod S, Purvee M, Benjamin D, Hafler D. Frequency analysis of CD4+CD8+ T cells cloned with IL-4. Cellular Immunology 1990, 125: 426-436. PMID: 2105169, DOI: 10.1016/0008-8749(90)90096-a.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, Differentiation, T-LymphocyteCD4 AntigensCD8 AntigensClone CellsCytotoxicity, ImmunologicHumansInterleukin-2Interleukin-4Recombinant ProteinsT-LymphocytesConceptsT cell clonesHigh-density CD4Expression of CD8RIL-4IL-2CD8 expressionT cellsIL-4CD8 moleculesCD4 expressionCell clonesPeripheral blood T cellsHigh density CD8Low CD8 expressionSurface CD8 expressionLectin-dependent cytotoxicitySurface of CD4Blood T cellsPattern of CD4Class I MHCNK activityPeripheral bloodCell surface expressionInflammatory responseCD8FcR-mediated crosslinking of Ta1 (CDw26) induces human T lymphocyte activation
Dang N, Hafler D, Schlossman S, Breitmeyer J. FcR-mediated crosslinking of Ta1 (CDw26) induces human T lymphocyte activation. Cellular Immunology 1990, 125: 42-57. PMID: 2152856, DOI: 10.1016/0008-8749(90)90061-u.Peer-Reviewed Original ResearchConceptsCD3/T cell receptor complexHuman T lymphocyte activationT lymphocyte activationT cellsT cell receptor complexCell receptor complexLymphocyte activationPeripheral blood T cellsMonoclonal antibodiesCytolytic effector functionExogenous IL-2Blood T cellsIL-2 receptorPositive accessory cellsT cell clonesT cell activationReceptor complexHuman T lymphocytesT cell regulatory networkAnti-Ta1Recall antigensPeripheral bloodIL-2T lymphocytesEffector functions
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 stimulationSequestration of virus-specific T cells in the cerebrospinal fluid of a patient with varicella zoster viral meningoencephalitis
Duby A, Weiner H, Benjamin D, Seidman JG, Hafler D. Sequestration of virus-specific T cells in the cerebrospinal fluid of a patient with varicella zoster viral meningoencephalitis. Journal Of Neuroimmunology 1989, 22: 63-68. PMID: 2465314, DOI: 10.1016/0165-5728(89)90010-6.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, Differentiation, T-LymphocyteDNAEpitopesHerpes ZosterHerpesvirus 3, HumanHistocompatibility Antigens Class IIHumansMaleMeningoencephalitisMiddle AgedNucleic Acid HybridizationPhenotypeT-LymphocytesConceptsT cell clonesVirus-specific T cellsT cellsCerebrospinal fluidViral meningoencephalitisImmune responseViral infectionHerpes zoster viral infectionAntigen-specific T cellsT-cell receptor beta-chain gene rearrangementBeta-chain gene rearrangementsT cell responsesPatient's cerebrospinal fluidSecondary immune responseT-cell antigen receptor beta-chain geneBeta-chain geneMyelin basic proteinVZV meningoencephalitisMumps virusMeningoencephalitisPatientsClonal expansionGene rearrangementsBlot analysisInfection