2007
Allelic variant in CTLA4 alters T cell phosphorylation patterns
Maier LM, Anderson DE, De Jager PL, Wicker LS, Hafler DA. Allelic variant in CTLA4 alters T cell phosphorylation patterns. Proceedings Of The National Academy Of Sciences Of The United States Of America 2007, 104: 18607-18612. PMID: 18000051, PMCID: PMC2141824, DOI: 10.1073/pnas.0706409104.Peer-Reviewed Original ResearchConceptsT cell antigen receptorAllelic variationMemory T cellsAutoimmune diseasesCell antigen receptorT cell signalingT cellsFunctional effectsDisease susceptibility allelesCell signalingPhosphorylation patternPhosphorylation levelsSusceptibility variantsTCR stimulationAllelic variantsHuman immune cellsAntigen receptorGenesImmune cellsHealthy individualsCTLA4 geneCellsSpecific mAbsCTLA4Disease
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 protein
2003
Rapamycin-resistant Proliferation of CD8+ T Cells Correlates with p27 kip1 Down-regulation and bcl-xL Induction, and Is Prevented by an Inhibitor of Phosphoinositide 3-Kinase Activity*
Slavik JM, Lim DG, Burakoff SJ, Hafler DA. Rapamycin-resistant Proliferation of CD8+ T Cells Correlates with p27 kip1 Down-regulation and bcl-xL Induction, and Is Prevented by an Inhibitor of Phosphoinositide 3-Kinase Activity*. Journal Of Biological Chemistry 2003, 279: 910-919. PMID: 14573608, DOI: 10.1074/jbc.m209733200.Peer-Reviewed Original ResearchMeSH KeywordsAnnexin A5Antibiotics, AntineoplasticBcl-X ProteinCD28 AntigensCD3 ComplexCD8-Positive T-LymphocytesCell Cycle ProteinsCell DivisionColoring AgentsCyclin DCyclin-Dependent Kinase Inhibitor p27CyclinsDose-Response Relationship, DrugDown-RegulationEnzyme InhibitorsEstersFluoresceinsHumansKineticsLymphocytesPhosphatidylinositol 3-KinasesProtein BindingProto-Oncogene Proteins c-bcl-2Signal TransductionSirolimusTime FactorsT-LymphocytesTumor Suppressor ProteinsConceptsInhibitor of phosphoinositideT cell receptorMammalian cell typesCell receptorBcl-xL inductionAction of rapamycinBcl-xL expressionT cellsHuman cellsCell survivalP27 Kip1Resistant proliferationCell typesPhosphoinositideHuman CD8RapamycinCellular proliferationEffect of rapamycinMicrobial infectionsCell populationsHigh-affinity T-cell receptorsSelective immunosuppressive effectT Cells CorrelateT cell populationsProliferationActivated CD8+ T cells in secondary progressive MS secrete lymphotoxin
Buckle GJ, Höllsberg P, Hafler DA. Activated CD8+ T cells in secondary progressive MS secrete lymphotoxin. Neurology 2003, 60: 702-705. PMID: 12601116, DOI: 10.1212/01.wnl.0000048204.89346.30.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntibodiesCD3 ComplexCD8-Positive T-LymphocytesCell DivisionCell SeparationCells, CulturedCytokinesFemaleFlow CytometryGene FrequencyHumansLymphotoxin-alphaMaleMiddle AgedMultiple Sclerosis, Chronic ProgressiveMultiple Sclerosis, Relapsing-RemittingPolymorphism, Single NucleotideReference ValuesConceptsT cellsNormal controlsSecondary progressive MSCytokine secretion profileFunctional activation statesLymphotoxin secretionProgressive MSActivated CD8Cytokine secretionSecretion profileCytokine genesCD8SecretionSignificant differencesPatientsSignificant increaseActivation stateSingle nucleotide polymorphism analysisPolymorphism analysisNucleotide polymorphism analysisCells
2001
Uncoupling p70s6 Kinase Activation and Proliferation: Rapamycin-Resistant Proliferation of Human CD8+ T Lymphocytes
Slavik J, Lim D, Burakoff S, Hafler D. Uncoupling p70s6 Kinase Activation and Proliferation: Rapamycin-Resistant Proliferation of Human CD8+ T Lymphocytes. The Journal Of Immunology 2001, 166: 3201-3209. PMID: 11207273, DOI: 10.4049/jimmunol.166.5.3201.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalCD2 AntigensCD28 AntigensCD3 ComplexCD8 AntigensCD8-Positive T-LymphocytesCell Line, TransformedClone CellsDose-Response Relationship, DrugDose-Response Relationship, ImmunologicDrug ResistanceEnzyme ActivationEpitopes, T-LymphocyteHLA-A AntigensHumansImmunosuppressive AgentsInterleukin-2Lymphocyte ActivationMajor Histocompatibility ComplexModels, ImmunologicalRibosomal Protein S6 KinasesSirolimusT-Lymphocyte SubsetsConceptsT cell clonesT cellsEffect of rapamycinHuman T cell responsesPeripheral blood T cellsCell clonesHeterogeneous proliferative responsesT cell responsesBlood T cellsT cell proliferationSpecific costimulatory signalsGraft infiltrationResistant proliferationInhibition of AgGraft rejectionHuman CD8IL-2RT lymphocytesProliferative responseCostimulatory signalsCell responsesPresence of rapamycinCell proliferationRapamycinProliferation
1999
Differential responses of invariant V alpha 24J alpha Q T cells and MHC class II-restricted CD4+ T cells to dexamethasone.
Milner J, Kent S, Ashley T, Wilson S, Strominger J, Hafler D. Differential responses of invariant V alpha 24J alpha Q T cells and MHC class II-restricted CD4+ T cells to dexamethasone. The Journal Of Immunology 1999, 163: 2522-9. PMID: 10452989, DOI: 10.4049/jimmunol.163.5.2522.Peer-Reviewed Original ResearchMeSH KeywordsAdjuvants, ImmunologicAntibodies, BlockingAntibodies, MonoclonalAntigens, CD1Antigens, CD1dAntigens, Differentiation, B-LymphocyteApoptosisAutocrine CommunicationCD3 ComplexCD4-Positive T-LymphocytesClone CellsDexamethasoneDose-Response Relationship, ImmunologicFas ReceptorHistocompatibility Antigens Class IIHumansImmunosuppressive AgentsInterleukin-2Lymphocyte ActivationReceptors, Antigen, T-Cell, alpha-betaSignal TransductionT-Lymphocyte SubsetsConceptsActivation-induced cell deathT cell clonesT cellsTCR signal strengthCell clonesAutocrine IL-2 productionNK T cellsT cell responsesT cell subsetsInhibition of CD4Anti-CD3 stimulationT cell proliferationEffect of dexamethasoneMHC class IIIL-2 productionPresence of dexamethasoneExogenous corticosteroidsCell subsetsImmunomodulatory consequencesDexamethasone treatmentImmune responseCD4High dosesLow dosesCell responses
1998
Differential 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
Expression of a hypoglycosylated form of CD86 (B7-2) on human T cells with altered binding properties to CD28 and CTLA-4.
Höllsberg P, Scholz C, Anderson DE, Greenfield EA, Kuchroo VK, Freeman GJ, Hafler DA. Expression of a hypoglycosylated form of CD86 (B7-2) on human T cells with altered binding properties to CD28 and CTLA-4. The Journal Of Immunology 1997, 159: 4799-805. PMID: 9366404, DOI: 10.4049/jimmunol.159.10.4799.Peer-Reviewed Original ResearchMeSH KeywordsAbataceptAnimalsAntibodies, MonoclonalAntigens, CDAntigens, DifferentiationB7-2 AntigenCD28 AntigensCD3 ComplexCD4-Positive T-LymphocytesCell Line, TransformedCHO CellsClone CellsCricetinaeCTLA-4 AntigenGlycosylationHumansImmunoconjugatesLymphocyte ActivationMembrane GlycoproteinsProtein BindingT-Lymphocyte SubsetsConceptsPost-translational modificationsCell type-specific post-translational modificationsHuman T cellsDifferent cell typesMajor costimulatory signalChinese hamster ovary cellsHamster ovary cellsCell clonesFusion proteinCostimulatory signalsCell typesT cell activationFunctional significanceOvary cellsBiochemical analysisSurface membraneCostimulatory functionDetectable bindingExpressionT cellsClonesCell activationCTLA-4-Ig fusion proteinCellsCell expression
1992
Early 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 ResearchConceptsAntigen-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, MessengerSirolimusTacrolimusT-LymphocytesConceptsT 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 chain
1991
Immunologic 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 ResearchConceptsT 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 pathwayFcR-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
Mechanisms 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, ImmunologicTetradecanoylphorbol AcetateT-LymphocytesTumor 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
1987
Phosphorylation of CD4 and CD8 molecules following T cell triggering.
Blue ML, Hafler DA, Craig KA, Levine H, Schlossman SF. Phosphorylation of CD4 and CD8 molecules following T cell triggering. The Journal Of Immunology 1987, 139: 3949-54. PMID: 2961801, DOI: 10.4049/jimmunol.139.12.3949.Peer-Reviewed Original ResearchConceptsCell receptor complexCD3-T cell receptor complexT cell triggeringReceptor complexPhorbol myristate acetate (PMA) treatmentMolecular signaling mechanismsDifferent receptor pathwaysErythrocyte binding proteinCD8 moleculesSignaling mechanismBinding proteinPhosphorylationCell triggeringT cell activationCD2 pathwayT cellsReceptor pathwayMolecular modificationsT cell clonesCell activationCell clonesPathwayActivationCD4Cells