2015
Biomarkers in multiple sclerosis
Housley WJ, Pitt D, Hafler DA. Biomarkers in multiple sclerosis. Clinical Immunology 2015, 161: 51-58. PMID: 26143623, DOI: 10.1016/j.clim.2015.06.015.Peer-Reviewed Original ResearchConceptsMultiple sclerosisB cell chemoattractant CXCL13Myelin-reactive T cellsMacrophage marker CD163Reactive T cellsMarkers of neurodegenerationKIR4.1 antibodiesMS seraClinical outcomesOligoclonal bandsYKL-40Disease progressionT cellsMS susceptibilityCerebrospinal fluidPotential biomarkersViral titersClinical useBiomarkersBiomarker researchSclerosisProgressionDisease diagnosisCD163CXCL13
2011
Increased Frequencies of Myelin Oligodendrocyte Glycoprotein/MHC Class II-Binding CD4 Cells in Patients with Multiple Sclerosis
Raddassi K, Kent SC, Yang J, Bourcier K, Bradshaw EM, Seyfert-Margolis V, Nepom GT, Kwok WW, Hafler DA. Increased Frequencies of Myelin Oligodendrocyte Glycoprotein/MHC Class II-Binding CD4 Cells in Patients with Multiple Sclerosis. The Journal Of Immunology 2011, 187: 1039-1046. PMID: 21653833, PMCID: PMC3131477, DOI: 10.4049/jimmunol.1001543.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAmino Acid SubstitutionCD4 Lymphocyte CountCD4-Positive T-LymphocytesCell CommunicationCell Line, TransformedCells, CulturedEpitopes, T-LymphocyteFemaleGene FrequencyHLA-DR AntigensHLA-DRB1 ChainsHumansImmunophenotypingMaleMiddle AgedMultiple SclerosisMyelin-Associated GlycoproteinMyelin-Oligodendrocyte GlycoproteinPeptide FragmentsProtein BindingProtein MultimerizationConceptsMyelin-reactive T cellsMultiple sclerosisT cell clonesT cellsHealthy controlsMOG-reactive T cellsAutoantigen-specific T cellsCell clonesStimulation of PMBCsClass II tetramersPathogenic immune cellsReactive T cellsSpecific T cellsMyelin oligodendrocyte glycoproteinHLA class IIBlood of subjectsT-cell cloning techniqueMOG peptidesShort-term cultureCD4 cellsMS subjectsAutoimmune diseasesPeripheral bloodControl subjectsOligodendrocyte glycoprotein
2008
Multiple Sclerosis and Regulatory T Cells
Costantino CM, Baecher-Allan C, Hafler DA. Multiple Sclerosis and Regulatory T Cells. Journal Of Clinical Immunology 2008, 28: 697-706. PMID: 18763026, PMCID: PMC2752287, DOI: 10.1007/s10875-008-9236-x.Peer-Reviewed Original ResearchConceptsRegulatory T cellsCentral nervous systemAutoreactive T cellsT cellsAntigen-specific Treg cellsAutoreactive effector T cellsAutoimmune tissue damageFrequency of TregsOrgan-specific autoimmunityEffector T cellsReactive T cellsBlood-brain barrierPathology of MSIntroductionMultiple sclerosisTreg cellsMS patientsPeripheral toleranceChronic inflammationMultiple sclerosisImmune disordersNew therapiesHealthy individualsNervous systemTissue damageDisease modelsMultiple Sclerosis and Regulatory T Cells
Hutton J, Baecher-Allan C, Hafler D. Multiple Sclerosis and Regulatory T Cells. 2008, 265-277. DOI: 10.1007/978-0-387-77909-6_13.Peer-Reviewed Original ResearchRegulatory T cellsAutoreactive T cellsMultiple sclerosisT cellsAntigen-specific Treg cellsImmunopathology of MSCentral nervous system white matterAutoimmune tissue damageFrequency of TregsNervous system white matterOrgan-specific autoimmunityEffector T cellsReactive T cellsImmunosuppressive therapyTreg cellsAutoimmune processMS patientsPeripheral toleranceSpecific autoimmunityImmune disordersNew therapiesHealthy individualsB cellsWhite matterTissue damage
2003
CTLA-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
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
Constitutive expression of costimulatory molecules by human microglia and its relevance to CNS autoimmunity
Dangond F, Windhagen A, Groves C, Hafler D. Constitutive expression of costimulatory molecules by human microglia and its relevance to CNS autoimmunity. Journal Of Neuroimmunology 1997, 76: 132-138. PMID: 9184642, DOI: 10.1016/s0165-5728(97)00043-x.Peer-Reviewed Original ResearchConceptsCentral nervous systemCostimulatory moleculesHuman microgliaMyelin-reactive T cellsTh1 T cell responsesExpression of B7.1Reactive T cellsT cell responsesMultiple sclerosis plaquesT cell surface moleculesB7.2 costimulatory moleculesMHC-antigen complexesT cell activationT cell receptorCNS autoimmunityCNS inflammationB7.2 expressionBiopsy specimensB7 familyT cellsNormal brainMicrogliaNervous systemB7.1High expression
1996
Induction of circulating myelin basic protein and proteolipid protein-specific transforming growth factor-beta1-secreting Th3 T cells by oral administration of myelin in multiple sclerosis patients.
Fukaura H, Kent SC, Pietrusewicz MJ, Khoury SJ, Weiner HL, Hafler DA. Induction of circulating myelin basic protein and proteolipid protein-specific transforming growth factor-beta1-secreting Th3 T cells by oral administration of myelin in multiple sclerosis patients. Journal Of Clinical Investigation 1996, 98: 70-77. PMID: 8690806, PMCID: PMC507402, DOI: 10.1172/jci118779.Peer-Reviewed Original ResearchConceptsMyelin basic proteinT cellsOral administrationAutoimmune diseasesTetanus toxoidT cell linesMS patientsMultiple sclerosisProteolipid proteinFrequency of MBPNon-treated MS patientsPLP-reactive T cellsTh1-type autoimmune diseaseShort-term T cell linesCell-mediated autoimmune diseaseRelapsing-remitting MS patientsOriginal T cell cloneSpecific IFN-gammaSystemic immune toleranceExperimental autoimmune diseasesRegulatory T cellsReactive T cellsIFN-gamma secretionMultiple sclerosis patientsT cell clones
1994
Clonal expansion and persistence of human T cells specific for an immunodominant myelin basic protein peptide.
Wucherpfennig KW, Zhang J, Witek C, Matsui M, Modabber Y, Ota K, Hafler DA. Clonal expansion and persistence of human T cells specific for an immunodominant myelin basic protein peptide. The Journal Of Immunology 1994, 152: 5581-92. PMID: 7514641, DOI: 10.4049/jimmunol.152.11.5581.Peer-Reviewed Original ResearchConceptsT cellsNormal subjectsImmunodominant myelin basic protein peptideMBP-specific T cell linesDR2 haplotypeSpecific T cell clonesTCR beta-chain sequencesReactive T cellsT cell responsesHLA-DR moleculesT cell clonesIdentical TCR sequencesMyelin basic protein peptideIL-2 stimulationT cell linesHuman T cellsAlpha-chain rearrangementMyelin basic proteinMultiple sclerosisBeta chain sequencesTCR rearrangementsPatientsCell responsesTCR alphaTCR sequencesStructural requirements for binding of an immunodominant myelin basic protein peptide to DR2 isotypes and for its recognition by human T cell clones.
Wucherpfennig KW, Sette A, Southwood S, Oseroff C, Matsui M, Strominger JL, Hafler DA. Structural requirements for binding of an immunodominant myelin basic protein peptide to DR2 isotypes and for its recognition by human T cell clones. Journal Of Experimental Medicine 1994, 179: 279-290. PMID: 7505801, PMCID: PMC2191316, DOI: 10.1084/jem.179.1.279.Peer-Reviewed Original ResearchConceptsT cell clonesMyelin basic proteinMultiple sclerosisCell clonesT cellsImmunodominant myelin basic protein peptideMBP-reactive T cellsMajor histocompatibility complex class IIDR2 haplotypeHistocompatibility complex class IIImmunodominant T cell epitopesHuman T cell clonesAutoreactive T cellsReactive T cellsT cell epitopesMyelin basic protein peptideT cell stimulationT cell receptorMS patientsDRB1 moleculesDR2 antigenRestriction elementsCell epitopesTarget antigenClass II
1993
MHC-Restricted Depletion of Human Myelin Basic Protein-Reactive T Cells by T Cell Vaccination
Zhang J, Medaer R, Stinissen P, Hafler D, Raus J. MHC-Restricted Depletion of Human Myelin Basic Protein-Reactive T Cells by T Cell Vaccination. Science 1993, 261: 1451-1454. PMID: 7690157, DOI: 10.1126/science.7690157.Peer-Reviewed Original ResearchConceptsAutoreactive T cellsT cell vaccinationT cellsT cell linesCell vaccinationMyelin basic protein-reactive T cellsRegulatory T cell linesMBP-reactive T cellsExperimental autoimmune diseasesReactive T cellsT cell responsesMajor histocompatibility antigensCell linesMyelin basic proteinMultiple sclerosisAutoimmune diseasesHistocompatibility antigensCell responsesVaccinationBasic proteinRecipientsPresent studyCellsCD8Sclerosis
1990
Shared Human T Cell Receptor Vβ Usage to Immunodominant Regions of Myelin Basic Protein
Wucherpfennig K, Ota K, Endo N, Seidman JG, Rosenzweig A, Weiner H, Hafler D. Shared Human T Cell Receptor Vβ Usage to Immunodominant Regions of Myelin Basic Protein. Science 1990, 248: 1016-1019. PMID: 1693015, DOI: 10.1126/science.1693015.Peer-Reviewed Original ResearchConceptsMultiple sclerosisImmunodominant regionMyelin basic proteinMS patientsT cellsBeta 17T cell receptor Vβ usageTCR V beta gene usageReactive T cellsBeta gene usageT cell receptor beta chainT cell linesBasic proteinSpecific immunotherapyVβ usageAutoimmune diseasesReceptor beta chainHealthy subjectsTarget antigenGene usageBeta 12Myelin proteinsTCR structureHuman MBPBeta chain