2004
Human CD4+CD25+ regulatory T cells
Baecher-Allan C, Viglietta V, Hafler DA. Human CD4+CD25+ regulatory T cells. Seminars In Immunology 2004, 16: 89-98. PMID: 15036232, DOI: 10.1016/j.smim.2003.12.005.Peer-Reviewed Original ResearchConceptsRegulatory T cellsT reg cellsT cellsT reg populationT cell subsetsT-reg functionHuman peripheral bloodIL-10Lymph nodesPeripheral bloodCell subsetsFunctional outcomeCord bloodTCR stimuliRapid effectsCellular compositionTCR signalsPotential involvementActivation stateStrong stimulationMiceBloodDisparate findingsCellsCulture conditions
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 TransductionSirolimusT-LymphocytesTime FactorsTumor 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 analysisCellsCTLA-4 dysregulation in the activation of myelin basic protein reactive T cells may distinguish patients with multiple sclerosis from healthy controls
Oliveira EM, Bar-Or A, Waliszewska AI, Cai G, Anderson DE, Krieger JI, Hafler DA. CTLA-4 dysregulation in the activation of myelin basic protein reactive T cells may distinguish patients with multiple sclerosis from healthy controls. Journal Of Autoimmunity 2003, 20: 71-81. PMID: 12604314, DOI: 10.1016/s0896-8411(02)00106-3.Peer-Reviewed Original ResearchConceptsMultiple sclerosisT cellsMyelin basic proteinHealthy controlsMyelin basic protein-reactive T cellsMBP-reactive T cellsPathogenesis of MSPeripheral blood mononuclear cellsCTLA-4 blockadeReactive T cellsBlood mononuclear cellsCo-stimulatory pathwaysNaïve T cellsCo-stimulatory signalsCentral nervous systemCTLA-4 engagementCytokine responsesAutoimmune responseMononuclear cellsInflammatory diseasesB7-CD28Proliferative responseNervous systemPatientsMyelin sheath
2002
GAD65-reactive T cells are activated in patients with autoimmune type 1a diabetes
Viglietta V, Kent SC, Orban T, Hafler DA. GAD65-reactive T cells are activated in patients with autoimmune type 1a diabetes. Journal Of Clinical Investigation 2002, 109: 895-903. PMID: 11927616, PMCID: PMC150925, DOI: 10.1172/jci14114.Peer-Reviewed Original ResearchMeSH KeywordsAbataceptAdultAntigens, CDAntigens, DifferentiationAutoimmunityB7-1 AntigenB7-2 AntigenCD28 AntigensCell DivisionCTLA-4 AntigenDiabetes Mellitus, Type 1FemaleGlutamate DecarboxylaseHumansImmunoconjugatesInterferon-gammaInterleukin-13IsoenzymesMaleMembrane GlycoproteinsSignal TransductionT-LymphocytesConceptsGAD65-reactive T cellsType 1 diabetesAutoreactive T cellsT cellsB7-1New-onset type 1 diabetesPancreatic islet cell antigensInsulin-dependent type 1 diabetesGlutamic acid decarboxylase 65B7-2 engagementType 1A diabetesMemory T cellsStimulation ex vivoIslet cell antigensB7-2 moleculesT cell proliferationB7-1 costimulationAutoimmune diseasesCTLA-4Healthy controlsPathogenic roleSelective blockadeCytokine secretionHuman diabetesT lymphocytes
2000
Glatiramer acetate (Copaxone®) induces degenerate, Th2-polarized immune responses in patients with multiple sclerosis
Duda PW, Schmied MC, Cook SL, Krieger JI, Hafler DA. Glatiramer acetate (Copaxone®) induces degenerate, Th2-polarized immune responses in patients with multiple sclerosis. Journal Of Clinical Investigation 2000, 105: 967-976. PMID: 10749576, PMCID: PMC377485, DOI: 10.1172/jci8970.Peer-Reviewed Original ResearchMeSH KeywordsAdultAmino Acid SequenceCell DivisionCells, CulturedCross ReactionsEpitopes, T-LymphocyteFemaleGlatiramer AcetateHumansImmunodominant EpitopesImmunosuppressive AgentsInterferon-gammaInterleukin-5Leukocytes, MononuclearLigandsMaleMiddle AgedMolecular Sequence DataMultiple SclerosisMyelin Basic ProteinMyelin SheathPeptide FragmentsPeptidesTetanus ToxoidTh2 CellsConceptsT cell responsesMultiple sclerosisGlatiramer acetateT cellsAntigen-specific T cell responsesTh2-polarized immune responseCross-reactive T cellsAlters immune functionHuman autoimmune diseasesAcetate inducesCross-reactive responsesT cell receptorT cell linesImmune deviationMost patientsTh2 typeAutoimmune disordersTh2 cytokinesAutoimmune diseasesDaily injectionsIL-13IL-5Th2 cellsHealthy subjectsImmune response
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
Cytokine secretion of myelin basic protein reactive T cells in patients with multiple sclerosis
Windhagen A, Anderson DE, Carrizosa A, Balashov K, Weiner HL, Hafler DA. Cytokine secretion of myelin basic protein reactive T cells in patients with multiple sclerosis. Journal Of Neuroimmunology 1998, 91: 1-9. PMID: 9846813, DOI: 10.1016/s0165-5728(98)00086-1.Peer-Reviewed Original ResearchConceptsMBP-reactive T cellsReactive T cellsChronic progressive multiple sclerosisProgressive multiple sclerosisMultiple sclerosisT cellsCytokine secretionMyelin basic proteinT cell linesNormal controlsMyelin basic protein-reactive T cellsAntigen-specific cytokine secretionMyelin-reactive T cellsNormal individualsShort-term T cell linesAutoreactive T cell linesCP MS patientsIL-12/IL-4/MBP-reactive cellsTh2-type phenotypeRR-MS patientsTh2 cytokine secretionAutoreactive T cellsMore IFN-gamma
1997
Variable Immortalizing Potential and Frequent Virus Latency in Blood-Derived T-Cell Clones Infected With Human T-Cell Leukemia Virus Type I
Richardson JH, Höllsberg P, Windhagen A, Child LA, Hafler DA, Lever A. Variable Immortalizing Potential and Frequent Virus Latency in Blood-Derived T-Cell Clones Infected With Human T-Cell Leukemia Virus Type I. Blood 1997, 89: 3303-3314. PMID: 9129036, DOI: 10.1182/blood.v89.9.3303.Peer-Reviewed Original ResearchConceptsT cell clonesHuman T-cell leukemia virus type IVirus type IT cellsSpontaneous proliferationFresh peripheral blood lymphocytesGag p24 productionCD4 T cellsInfected cellsPeripheral blood lymphocytesHTLV-I provirusViral mRNA expressionType IP24 productionVirus-cell interactionsIL-6Virus carriersInterleukin-6Blood lymphocytesHost cell factorsCytokine mRNAVirus latencyVirus-producing clonesHTLVMRNA expressionB7.2 expressed by T cells does not induce CD28-mediated costimulatory activity but retains CTLA4 binding: implications for induction of antitumor immunity to T cell tumors.
Greenfield EA, Howard E, Paradis T, Nguyen K, Benazzo F, McLean P, Höllsberg P, Davis G, Hafler DA, Sharpe AH, Freeman GJ, Kuchroo VK. B7.2 expressed by T cells does not induce CD28-mediated costimulatory activity but retains CTLA4 binding: implications for induction of antitumor immunity to T cell tumors. The Journal Of Immunology 1997, 158: 2025-34. PMID: 9036945, DOI: 10.4049/jimmunol.158.5.2025.Peer-Reviewed Original ResearchMeSH KeywordsAbataceptAnimalsAntigens, CDAntigens, DifferentiationB7-2 AntigenCD28 AntigensCell DivisionCTLA-4 AntigenFemaleImmunoconjugatesLymphocyte ActivationMembrane GlycoproteinsMiceMice, Inbred BALB CMice, Inbred C57BLProtein BindingT-LymphocytesThymomaThymus NeoplasmsTransfectionTumor Cells, Cultured
1995
Differential activation of proliferation and cytotoxicity in human T-cell lymphotropic virus type I Tax-specific CD8 T cells by an altered peptide ligand.
Höllsberg P, Weber WE, Dangond F, Batra V, Sette A, Hafler DA. Differential activation of proliferation and cytotoxicity in human T-cell lymphotropic virus type I Tax-specific CD8 T cells by an altered peptide ligand. Proceedings Of The National Academy Of Sciences Of The United States Of America 1995, 92: 4036-4040. PMID: 7732026, PMCID: PMC42097, DOI: 10.1073/pnas.92.9.4036.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceB-LymphocytesBinding SitesCD8-Positive T-LymphocytesCell DivisionCell Line, TransformedCytotoxicity, ImmunologicGene Products, taxHerpesvirus 4, HumanHLA-A2 AntigenHuman T-lymphotropic virus 1HumansKineticsLymphocyte ActivationMolecular Sequence DataMutagenesis, Site-DirectedPoint MutationThymidineConceptsCD8 T cellsInterleukin-2 secretionT cell receptor contact residuesT cellsReceptor contact residuesCD8 T cell clonesCytotoxic CD8 T cellsMyelopathy/tropical spastic paraparesisT cell-mediated cytotoxicityHAM/TSPTropical spastic paraparesisT cell clonesAltered peptide ligandT cell-mediated cytolysisHuman T-cell leukemia virus type IT cell stimulationVirus type IAnalog peptidesHLA-A2Spastic paraparesisNeurologic diseaseSecondary stimulationSecondary responsePeptide antigensPrimary activation
1985
Phenotypic and functional analysis of T cells cloned directly from the blood and cerebrospinal fluid of patients with multiple sclerosis
Hafler D, Buchsbaum M, Johnson D, Weiner H. Phenotypic and functional analysis of T cells cloned directly from the blood and cerebrospinal fluid of patients with multiple sclerosis. Annals Of Neurology 1985, 18: 451-458. PMID: 2416267, DOI: 10.1002/ana.410180407.Peer-Reviewed Original ResearchConceptsMultiple sclerosisBlood of patientsT cellsMyelin basic proteinCerebrospinal fluid lymphocytesT-cell abnormalitiesCSF of patientsAntigen-specific cellsIndividual T cellsBasic proteinSuppressor cellsViral meningoencephalitisStimulating lymphocytesInterleukin-2Antigen reactivityCell abnormalitiesCerebrospinal fluidSingle cell clonal analysisPatientsT8 populationWhite matterBloodCSFSclerosisLymphocytes