2010
IL-12 induces human CD4+CD45RA-CD25hiCD127low/neg regulatory T cells to secrete IFNγ and IL-10 and acquire a non-regulatory effector phenotype (138.9)
Dominguez-Villar M, Hafler D, Baecher-Allan C. IL-12 induces human CD4+CD45RA-CD25hiCD127low/neg regulatory T cells to secrete IFNγ and IL-10 and acquire a non-regulatory effector phenotype (138.9). The Journal Of Immunology 2010, 184: 138.9-138.9. DOI: 10.4049/jimmunol.184.supp.138.9.Peer-Reviewed Original ResearchRegulatory T cellsT cellsEffector phenotypeTreg functionIL-10Immune responseHuman Treg functionCD4 T cellsT cell responsesIL-12 familyIL-12 inducesTreg suppressionPeripheral toleranceCytokine milieuT-betIFN-gammaTregsImmune systemCell responsesCytokinesRecent evidencePivotal roleCellsPhenotypeDistinct effects
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
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
2004
PD-1 ligands, negative regulators for activation of naïve, memory, and recently activated human CD4+ T cells
Cai G, Karni A, Oliveira EM, Weiner HL, Hafler DA, Freeman GJ. PD-1 ligands, negative regulators for activation of naïve, memory, and recently activated human CD4+ T cells. Cellular Immunology 2004, 230: 89-98. PMID: 15598424, DOI: 10.1016/j.cellimm.2004.09.004.Peer-Reviewed Original ResearchConceptsPD-1 ligand blockadeT cellsPD-L1Myelin basic proteinPD-L2Human CD4Ex vivo dendritic cellsVivo dendritic cellsPD-1 ligandsPD-1 pathwayPrimary responseActivation of naïveNaive T cellsPD-1Dendritic cellsCytokine productionNormal donorsIFN-gammaSecondary responseCD4BlockadeHigh expressionNegative regulatory pathwaysInduced activationBasic proteinDisease‐related epitope spread in a humanized T cell receptor transgenic model of multiple sclerosis
Ellmerich S, Takacs K, Mycko M, Waldner H, Wahid F, Boyton RJ, Smith PA, Amor S, Baker D, Hafler DA, Kuchroo VK, Altmann DM. Disease‐related epitope spread in a humanized T cell receptor transgenic model of multiple sclerosis. European Journal Of Immunology 2004, 34: 1839-1848. PMID: 15214032, DOI: 10.1002/eji.200324044.Peer-Reviewed Original ResearchConceptsHLA-DR15Multiple sclerosisTransgenic modelT cell receptor transgenic modelHLA class II moleculesHuman T cell clonesInduction of paralysisPoverty of movementHLA class IIT cell clonesClass II moleculesHuman TCR specificMBP 85Specific immunotherapyTCR specificMyelin epitopesT cellsIFN-gammaRodent modelsDiseaseCell clonesEpitopesDisease phenotypeSclerosisImmunization
2001
Molecular Mimicry in Lyme Arthritis Demonstrated at the Single Cell Level: LFA-1αL Is a Partial Agonist for Outer Surface Protein A-Reactive T Cells
Trollmo C, Meyer A, Steere A, Hafler D, Huber B. Molecular Mimicry in Lyme Arthritis Demonstrated at the Single Cell Level: LFA-1αL Is a Partial Agonist for Outer Surface Protein A-Reactive T Cells. The Journal Of Immunology 2001, 166: 5286-5291. PMID: 11290815, DOI: 10.4049/jimmunol.166.8.5286.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, SurfaceBacterial Outer Membrane ProteinsBacterial VaccinesBorrelia burgdorferi GroupClone CellsHumansHybridomasLipoproteinsLyme DiseaseLyme Disease VaccinesLymphocyte ActivationLymphocyte Function-Associated Antigen-1MiceMice, TransgenicMolecular MimicryPeptide FragmentsT-Lymphocyte SubsetsConceptsIL-13Antibiotic treatment-resistant Lyme arthritisPartial agonistTreatment-resistant Lyme arthritisChronic inflammatory joint diseaseT cell hybridsDR4 transgenic miceHuman T cell clonesClass II tetramersInflammatory joint diseaseSymptoms of arthritisT cell responsesT cell levelsEpisodes of arthritisT cell clonesSurface protein AAutoimmune mechanismsOuter surface protein ALyme arthritisJoint diseaseT cellsIFN-gammaImmunodominant epitopesCell levelTransgenic mice
2000
Direct enumeration of Borrelia-reactive CD4 T cells ex vivo by using MHC class II tetramers
Meyer A, Trollmo C, Crawford F, Marrack P, Steere A, Huber B, Kappler J, Hafler D. Direct enumeration of Borrelia-reactive CD4 T cells ex vivo by using MHC class II tetramers. Proceedings Of The National Academy Of Sciences Of The United States Of America 2000, 97: 11433-11438. PMID: 11005833, PMCID: PMC17217, DOI: 10.1073/pnas.190335897.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, SurfaceBacterial Outer Membrane ProteinsBacterial VaccinesBiopolymersBorrelia burgdorferi GroupCD4-Positive T-LymphocytesClone CellsCytokinesDose-Response Relationship, ImmunologicHLA-DR AntigensHLA-DRB1 ChainsHumansIn Vitro TechniquesLipoproteinsLyme DiseaseLyme Disease VaccinesConceptsClass II tetramersMHC class II tetramersT cellsSynovial fluidPeripheral bloodMajor histocompatibility complex class II tetramersTreatment-resistant Lyme arthritisAntigen-reactive T cellsCD4 T cellsDifferent cytokine profilesIL-13 secretionT cell clonesAllogeneic feeder cellsCytokine profileLyme arthritisInflammatory compartmentIL-2IFN-gammaImmunodominant epitopesCell clonesBorrelia burgdorferiPatientsHLABloodCellsA 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
HTLV-I-Infected T Cells Evade the Antiproliferative Action of IFN-β
Smith D, Buckle G, Hafler D, Frank D, Höllsberg P. HTLV-I-Infected T Cells Evade the Antiproliferative Action of IFN-β. Virology 1999, 257: 314-321. PMID: 10329542, DOI: 10.1006/viro.1999.9679.Peer-Reviewed Original ResearchConceptsT cell clonesIFN-betaT cellsAntiproliferative actionHuman T-cell lymphotropic virus type IMyelopathy/tropical spastic paraparesisLymphotropic virus type INormal immunoregulatory mechanismsInnate immune defense mechanismsHost T cellsExogenous IL-2Tropical spastic paraparesisT cell proliferationImmune defense mechanismsVirus type IT cell activationPathogenesis of HTLVImmunoregulatory mechanismsSpastic paraparesisIL-2Phosphorylation of STAT1IFN-gammaViral infectionHigh dosesHTLV
1998
Identification of a T cell subset capable of both IFN-gamma and IL-10 secretion in patients with chronic Borrelia burgdorferi infection.
Pohl-Koppe A, Balashov K, Steere A, Logigian E, Hafler D. Identification of a T cell subset capable of both IFN-gamma and IL-10 secretion in patients with chronic Borrelia burgdorferi infection. The Journal Of Immunology 1998, 160: 1804-10. PMID: 9469440, DOI: 10.4049/jimmunol.160.4.1804.Peer-Reviewed Original ResearchConceptsT cell linesIFN-gamma/ILB. burgdorferi infectionIFN-gammaBurgdorferi infectionT cellsIL-12Lyme patientsCell linesLyme diseaseVigorous humoral immune responseIL-10 secretionExogenous IL-12T cell subsetsT cell populationsHumoral immune responseNovel populationB. burgdorferiBorrelia burgdorferi infectionPrecursor T cellsWhole mononuclear cellsHuman T cellsGroups of subjectsIL-10Cell subsetsDifferential 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
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