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
2010
TGF-β Induces IL-9 Production from Human Th17 Cells
Beriou G, Bradshaw EM, Lozano E, Costantino CM, Hastings WD, Orban T, Elyaman W, Khoury SJ, Kuchroo VK, Baecher-Allan C, Hafler DA. TGF-β Induces IL-9 Production from Human Th17 Cells. The Journal Of Immunology 2010, 185: 46-54. PMID: 20498357, PMCID: PMC2936106, DOI: 10.4049/jimmunol.1000356.Peer-Reviewed Original ResearchMeSH KeywordsAdultCell PolarityCells, CulturedCoculture TechniquesDiabetes Mellitus, Type 1Gene Expression RegulationHumansImmunohistochemistryInflammation MediatorsInterleukin-17Interleukin-9Middle AgedResting Phase, Cell CycleT-Lymphocytes, Helper-InducerTransforming Growth Factor beta1Young AdultConceptsCD4 T cellsIL-9 productionIL-17IL-9IL-1betaCD4 cellsProinflammatory cytokinesT cellsNaive cellsIL-9/ILCD4 T cell subsetsMemory CD4 T cellsNaive CD4 T cellsHuman naive CD4 T cellsTh17-inducing cytokinesT cell subsetsHuman autoimmune diseasesAutoimmune diabetesMemory CD4Th17 cellsTh2 cytokinesAutoimmune diseasesCell subsetsIL-4Inflammatory conditions
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 Research
2006
MHC Class II Expression Identifies Functionally Distinct Human Regulatory T Cells
Baecher-Allan C, Wolf E, Hafler DA. MHC Class II Expression Identifies Functionally Distinct Human Regulatory T Cells. The Journal Of Immunology 2006, 176: 4622-4631. PMID: 16585553, DOI: 10.4049/jimmunol.176.8.4622.Peer-Reviewed Original ResearchConceptsContact-dependent suppressionRegulatory T cellsT cellsCD4 cellsDR expressionFunctional MHC class II moleculesRegulatory T cell populationHuman regulatory T cellsMHC class II determinantsIL-10 secretionClass II determinantsMHC class II moleculesHigh Foxp3 expressionMHC-II expressionEarly IL-4T cell populationsT cell nonresponsivenessClass II moleculesEx vivo expressionVivo expressionHuman CD4 cellsSubpopulations CD4Treg populationFoxp3 expressionIL-4
2005
Loss of IL-4 Secretion from Human Type 1a Diabetic Pancreatic Draining Lymph Node NKT Cells
Kent SC, Chen Y, Clemmings SM, Viglietta V, Kenyon NS, Ricordi C, Hering B, Hafler DA. Loss of IL-4 Secretion from Human Type 1a Diabetic Pancreatic Draining Lymph Node NKT Cells. The Journal Of Immunology 2005, 175: 4458-4464. PMID: 16177088, DOI: 10.4049/jimmunol.175.7.4458.Peer-Reviewed Original ResearchConceptsT cell clonesINKT cell clonesINKT cellsIL-4Cell clonesNKT cellsLymph nodesCytokine secretionIFN-gammaHuman type 1AType 1AIslet-infiltrating CD4Invariant NKT cellsT cell primingIL-4 secretionRegulation of murineSite of drainageRegulatory cellsDiabetic subjectsCell primingT cellsDiabetic samplesAltered frequencyTCR stimulationSecretion
2001
Decreases in Interleukin-4 Secretion by Invariant CD4−CD8−Vα24JαQ T Cells in Peripheral Blood of Patients with Relapsing–Remitting Multiple Sclerosis
Gausling R, Trollmo C, Hafler D. Decreases in Interleukin-4 Secretion by Invariant CD4−CD8−Vα24JαQ T Cells in Peripheral Blood of Patients with Relapsing–Remitting Multiple Sclerosis. Clinical Immunology 2001, 98: 11-17. PMID: 11141321, DOI: 10.1006/clim.2000.4942.Peer-Reviewed Original ResearchConceptsRelapsing-remitting multiple sclerosisT cell receptorIFN-gamma secretionMultiple sclerosisT cell clonesT cellsCytokine profilePeripheral bloodIL-4Cell clonesProgressive multiple sclerosisRR-MS patientsCytokine secretion patternsRelapsing-remitting MSInterleukin-4 secretionT cell functionalityCytokine secretionHealthy controlsSecretion patternPatientsCP-MSImmune systemControl individualsCell receptorSecretionHeterophile Antibodies Indicate Progression of Autoimmunity in Human Type 1 Diabetes Mellitus Before Clinical Onset
Orban T, Kent SC, Malik P, Milner JD, Schuster K, Jackson RA, Hafler DA. Heterophile Antibodies Indicate Progression of Autoimmunity in Human Type 1 Diabetes Mellitus Before Clinical Onset. Autoimmunity 2001, 34: 247-264. PMID: 11905851, DOI: 10.3109/08916930109014694.Peer-Reviewed Original ResearchConceptsHeterophile antibodiesType 1 diabetes autoimmunityType 1 diabetes mellitus patientsDiabetes mellitus patientsProgression of autoimmunityAntibody-positive seraType 1 diabetesFirst-degree relativesHuman type 1T cell growthAnti-human immunoglobulinDiabetes autoimmunitySerum cytokinesMellitus patientsClinical onsetAntibody presenceIL-4Degree relativesDisease progressionLower incidenceHigh riskHigh incidenceHeterophilic antibodiesAntibody activityAntibody reactivity
2000
A novel population of B7‐1+ T cells producing intracellular IL‐4 is decreased in patients with multiple sclerosis
Kipp B, Bar‐Or A, Gausling R, Oliveira E, Fruhan S, Stuart W, Hafler D. A novel population of B7‐1+ T cells producing intracellular IL‐4 is decreased in patients with multiple sclerosis. European Journal Of Immunology 2000, 30: 2092-2100. PMID: 10940899, DOI: 10.1002/1521-4141(200007)30:7<2092::aid-immu2092>3.0.co;2-7.Peer-Reviewed Original ResearchConceptsT cell receptorIntracellular IL-4Multiple sclerosisT cellsB7-1IL-4Autoimmune diseasesTNF-alphaIFN-gammaIL-4-producing T cellsLittle IL-4Immunoregulatory T cellsIL-4 productionIntracellular IFN-gammaT cell populationsLittle IFN-gammaNovel populationDiverse TCR repertoireMHC class IIHuman T cellsShort-term cultureCell surface moleculesTCR repertoireNormal subjectsPatients
1999
Heterophile antibodies segregate in families and are associated with protection from type 1 diabetes
She J, Ellis T, Wilson S, Wasserfall C, Marron M, Reimsneider S, Kent S, Hafler D, Neuberg D, Muir A, Strominger J, Atkinson M. Heterophile antibodies segregate in families and are associated with protection from type 1 diabetes. Proceedings Of The National Academy Of Sciences Of The United States Of America 1999, 96: 8116-8119. PMID: 10393957, PMCID: PMC22197, DOI: 10.1073/pnas.96.14.8116.Peer-Reviewed Original ResearchCross-Reactivity of T-Cell Clones Specific for Altered Peptide Ligands of Myelin Basic Protein
Ausubel L, Bieganowska K, Hafler D. Cross-Reactivity of T-Cell Clones Specific for Altered Peptide Ligands of Myelin Basic Protein. Cellular Immunology 1999, 193: 99-107. PMID: 10202117, DOI: 10.1006/cimm.1998.1447.Peer-Reviewed Original ResearchConceptsT cell clonesT cellsSpecific T cell repertoireAutoreactive T cellsTh1-type cytokinesTh2-type cytokinesMultiple sclerosis patientsT cell repertoireAltered peptide ligandT cell receptor alphaPotential beneficial effectsTCR contact residuesMyelin basic proteinDownregulatory cytokinesSclerosis patientsIL-4IL-5Individual patientsReceptor alphaBeneficial effectsClonal expansionCytokinesPeptide ligandsSubstantial proliferationCross reactivity
1998
Myelin basic protein reactive Th2 T cells are found in acute disseminated encephalomyelitis
Pohl-Koppe A, Burchett S, Thiele E, Hafler D. Myelin basic protein reactive Th2 T cells are found in acute disseminated encephalomyelitis. Journal Of Neuroimmunology 1998, 91: 19-27. PMID: 9846815, DOI: 10.1016/s0165-5728(98)00125-8.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, ViralAutoimmunityChildChild, PreschoolDemyelinating DiseasesEncephalomyelitis, Acute DisseminatedEncephalomyelitis, Autoimmune, ExperimentalEpitopesFemaleHerpes ZosterHerpesvirus 3, HumanHumansInfantInterferon-gammaInterleukin-2Interleukin-4MaleMyelin Basic ProteinT-LymphocytesConceptsAcute disseminated encephalomyelitisMBP-reactive T cell linesCentral nervous systemT cellsIL-4T cell linesDisseminated encephalomyelitisSignificant IFN-gamma secretionMyelin-reactive T cellsIFN-gamma secretionIL-4 secretionTh2 T cellsCell linesAutoimmune diseasesPredominant cytokineNormal subjectsSpontaneous recoveryNervous systemPatientsEncephalomyelitisCytokinesSecretionRecovery phaseCellsSubjectsExtreme Th1 bias of invariant Vα24JαQ T cells in type 1 diabetes
Wilson S, Kent S, Patton K, Orban T, Jackson R, Exley M, Porcelli S, Schatz D, Atkinson M, Balk S, Strominger J, Hafler D. Extreme Th1 bias of invariant Vα24JαQ T cells in type 1 diabetes. Nature 1998, 391: 177-181. PMID: 9428763, DOI: 10.1038/34419.Peer-Reviewed Original ResearchConceptsType 1 diabetesT cellsMajor histocompatibility complexIL-4T cell-mediated destructionNon-diabetic siblingsAutoreactive T cellsHigher serum levelsTwins/tripletsType1 diabetic patientsDiabetic patientsSerum levelsTh1 biasDiabetic siblingsImmune systemTissue damageIncomplete concordanceDiabetesHistocompatibility complexIDDMIdentical twinsIFNDiseaseRiskCellsDifferential Display Cloning of a Novel Human Histone Deacetylase (HDAC3) cDNA from PHA-Activated Immune Cells
Dangond F, Hafler D, Tong J, Randall J, Kojima R, Utku N, Gullans S. Differential Display Cloning of a Novel Human Histone Deacetylase (HDAC3) cDNA from PHA-Activated Immune Cells. Biochemical And Biophysical Research Communications 1998, 242: 648-652. PMID: 9464271, DOI: 10.1006/bbrc.1997.8033.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceBlotting, NorthernCD3 ComplexCell CycleCloning, MolecularDNAFlow CytometryGene Expression Regulation, EnzymologicGranulocyte-Macrophage Colony-Stimulating FactorHistone DeacetylasesHumansMolecular Sequence DataPhylogenyPhytohemagglutininsRNA, MessengerSequence AlignmentSequence Analysis, DNAT-LymphocytesTransfectionTumor Cells, CulturedConceptsPeripheral blood mononuclear cellsBlock T cell proliferationEffects of HDACsBlood mononuclear cellsT cell proliferationT cell clonesG2/M cell accumulationNon-immune tissuesTHP-1 cellsHDAC mRNAsPBMC levelsDifferential display cloningMononuclear cellsIL-4Immune cellsIFN-gammaAlpha CD3Histone acetyltransferasesCell accumulationHDAC3 mRNAHDAC inhibitorsHistone deacetylase assayCell clonesCell cycle progressionFunctional activity
1997
Immune deviation following pulse cyclophosphamide/methylprednisolone treatment of multiple sclerosis: Increased interleukin‐4 production and associated eosinophilia
Smith D, Balashov K, Hafler D, Khoury S, Weiner H. Immune deviation following pulse cyclophosphamide/methylprednisolone treatment of multiple sclerosis: Increased interleukin‐4 production and associated eosinophilia. Annals Of Neurology 1997, 42: 313-318. PMID: 9307252, DOI: 10.1002/ana.410420307.Peer-Reviewed Original ResearchConceptsMonthly intravenous methylprednisolonePulse cyclophosphamide therapyMultiple sclerosisImmune deviationIL-4Cyclophosphamide therapyIFN-beta1bMS patientsHealthy controlsTh1-type cell-mediated autoimmune diseaseCell-mediated autoimmune diseaseMethotrexate-treated patientsT-cell interferonUntreated MS patientsUntreated multiple sclerosisPeripheral blood eosinophiliaProgressive MS patientsTh2-type responseCyclophosphamide-treated patientsIL-10 productionInterleukin-4 productionMinimal IL-4Intravenous cyclophosphamideIntravenous methylprednisoloneBlood eosinophilia
1996
Activation of human T cell lymphotropic virus type I-infected T cells is independent of B7 costimulation.
Scholz C, Freeman GJ, Greenfield EA, Hafler DA, Höllsberg P. Activation of human T cell lymphotropic virus type I-infected T cells is independent of B7 costimulation. The Journal Of Immunology 1996, 157: 2932-8. PMID: 8816399, DOI: 10.4049/jimmunol.157.7.2932.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalAntigen-Presenting CellsAntigens, CDAutoimmunityB7-1 AntigenB7-2 AntigenBase SequenceCD28 AntigensCHO CellsClone CellsCricetinaeCricetulusEnzyme ActivationHLA-DR AntigensHLA-DRB1 ChainsHuman T-lymphotropic virus 1HumansInterferon-gammaInterleukin-4Interleukin-5Janus Kinase 3Lymphocyte ActivationMembrane GlycoproteinsMolecular Sequence DataMyelin Basic ProteinProtein-Tyrosine KinasesSignal TransductionT-Lymphocyte SubsetsTransfectionConceptsHuman T-cell lymphotropic virus type ILymphotropic virus type IB7 costimulationT cell clonesT cellsB7-1Virus type IIL-4IL-5B7-2IFN-gammaAutoreactive T cell responsesCell clonesAg-specific signalAutoimmune-like diseaseT cell responsesAutoreactive T cellsHTLV-I infectionB7-2 costimulationB7-2 moleculesUninfected T cellsType IAutoimmune responseB7 expressionCytokine secretionIL-12 induces human T cells secreting IL-10 with IFN-gamma.
Windhagen A, Anderson DE, Carrizosa A, Williams RE, Hafler DA. IL-12 induces human T cells secreting IL-10 with IFN-gamma. The Journal Of Immunology 1996, 157: 1127-31. PMID: 8757617, DOI: 10.4049/jimmunol.157.3.1127.Peer-Reviewed Original ResearchConceptsIL-10T cell responsesIL-12T cell clonesIFN-gammaT cellsT cell linesHuman T cellsMyelin basic protein-reactive T cell clonesCell responsesPredominant T cell responseShort-term T cell linesConcomitant secretionHuman T cell responsesCell clonesAg-specific stimulationIFN-gamma secretionIFN-gamma productionAnti-CD3 mAbCell linesMyelin basic proteinGamma AbIL-2IL-4Cytokine secretionAntigen‐specific TGF‐β1 Secretion with Bovine Myelin Oral Tolerization in Multiple Sclerosis
FUKAURA H, KENT S, PIETRUSEWICZ M, KHOURY S, WEINER H, HAFLER D. Antigen‐specific TGF‐β1 Secretion with Bovine Myelin Oral Tolerization in Multiple Sclerosis. Annals Of The New York Academy Of Sciences 1996, 778: 251-257. PMID: 8610978, DOI: 10.1111/j.1749-6632.1996.tb21133.x.Peer-Reviewed Original ResearchConceptsRelapsing-remitting MS patientsHuman autoimmune diseasesOral tolerizationMultiple sclerosisAutoimmune diseasesT cell linesMS patientsCytokine secretionT cellsAutoreactive T-cell populationsAutoreactive T cellsT cell populationsT-cell fractionCNS white matterFed patientsIL-4Inflammatory responseΒ1 secretionIFN-gammaTolerizationWhite matterPatientsSclerosisBovine myelinSecretion
1995
Modulation of cytokine patterns of human autoreactive T cell clones by a single amino acid substitution of their peptide ligand
Windhagen A, Schooz C, Höllsberg P, Fukaura H, Sette A, Hafler D. Modulation of cytokine patterns of human autoreactive T cell clones by a single amino acid substitution of their peptide ligand. Immunity 1995, 2: 373-380. PMID: 7536622, DOI: 10.1016/1074-7613(95)90145-0.Peer-Reviewed Original ResearchConceptsT cell clonesCytokine patternCell clonesHuman autoreactive T cell clonesT cell cytokine secretionAutoreactive T cell clonesT cell receptor contact residuesIL-4 secretionAltered peptide ligandMajor histocompatability complexPresence of ionomycinMyelin basic proteinIL-10Receptor contact residuesIL-4IL-2TCR antagonistsCytokine secretionImmune responseIFN-gammaPeptide ligandsProtein secretionCalcium fluxMature T-cell clonesSecretion
1991
Restricted T cell expression of IL-2/IFN-gamma mRNA in human inflammatory disease.
Brod SA, Benjamin D, Hafler DA. Restricted T cell expression of IL-2/IFN-gamma mRNA in human inflammatory disease. The Journal Of Immunology 1991, 147: 810-5. PMID: 1907306, DOI: 10.4049/jimmunol.147.3.810.Peer-Reviewed Original ResearchConceptsPeripheral bloodCSF of subjectsIL-5 mRNAT cell clonesIFN-gamma mRNAIL-4Inflammatory diseasesIFN-gammaIL-2Systemic inflammationT cellsTh1 T cell clonesTh2-type T cellsT cell cytokine profilesIL-2/ILDistinct T cell populationsCell clonesT cell populationsT cell expressionType T cellsTNF-alpha mRNAHuman inflammatory diseasesIL-2 mRNACytokine profileImmune compartment
1990
Frequency 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 ResearchConceptsT 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 responseCD8