2023
Differential effects of anti-CD20 therapy on CD4 and CD8 T cells and implication of CD20-expressing CD8 T cells in MS disease activity
Shinoda K, Li R, Rezk A, Mexhitaj I, Patterson K, Kakara M, Zuroff L, Bennett J, von Büdingen H, Carruthers R, Edwards K, Fallis R, Giacomini P, Greenberg B, Hafler D, Ionete C, Kaunzner U, Lock C, Longbrake E, Pardo G, Piehl F, Weber M, Ziemssen T, Jacobs D, Gelfand J, Cross A, Cameron B, Musch B, Winger R, Jia X, Harp C, Herman A, Bar-Or A. Differential effects of anti-CD20 therapy on CD4 and CD8 T cells and implication of CD20-expressing CD8 T cells in MS disease activity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2207291120. PMID: 36634138, PMCID: PMC9934304, DOI: 10.1073/pnas.2207291120.Peer-Reviewed Original ResearchConceptsEarly disease activityDisease activityCD8 T cellsT cellsCD20 therapyPeripheral blood mononuclear cellsCellular immune profilesNew disease activityMS disease activityT cell poolMultiple sclerosis patientsAnti-inflammatory profileBlood mononuclear cellsTreatment-associated changesMultiparametric flow cytometryCentral nervous systemFurther dosingRepeat infusionsImmune profileMS patientsSclerosis patientsValidation cohortMononuclear cellsRelapse developmentImmune cascade
2016
Multiple sclerosis
Axisa PP, Hafler DA. Multiple sclerosis. Current Opinion In Neurology 2016, 29: 345-353. PMID: 27058221, PMCID: PMC7882195, DOI: 10.1097/wco.0000000000000319.Peer-Reviewed Original ResearchConceptsMultiple sclerosisGenome-wide association studiesAssociation studiesMultiple sclerosis (MS) etiologyMultiple sclerosis progressionMultiple sclerosis patientsHigh-throughput genetic analysisImmune cell functionNumerous candidate biomarkersWide association studyMechanisms of neurodegenerationImmunomodulatory treatmentSclerosis patientsClinical outcomesTreatment arsenalDisease progressionImmune regulationSclerosisNew biomarkersCandidate biomarkersPatient careGenetic variationGenetic analysisCell functionProgression
2013
PhIP-Seq characterization of autoantibodies from patients with multiple sclerosis, type 1 diabetes and rheumatoid arthritis
Larman HB, Laserson U, Querol L, Verhaeghen K, Solimini NL, Xu GJ, Klarenbeek PL, Church GM, Hafler DA, Plenge RM, Nigrovic PA, De Jager PL, Weets I, Martens GA, O'Connor KC, Elledge SJ. PhIP-Seq characterization of autoantibodies from patients with multiple sclerosis, type 1 diabetes and rheumatoid arthritis. Journal Of Autoimmunity 2013, 43: 1-9. PMID: 23497938, PMCID: PMC3677742, DOI: 10.1016/j.jaut.2013.01.013.Peer-Reviewed Original ResearchConceptsType 1 diabetes patientsRheumatoid arthritis patientsMultiple sclerosis patientsLoss of tolerancePhage immunoprecipitation sequencingType 1 diabetesNeurological autoimmunitySeropositivity statusArthritis patientsRheumatoid arthritisSclerosis patientsMultiple sclerosisAutoimmune diseasesDiabetes patientsCerebrospinal fluidGeneral populationSynovial fluidHealthy seraPatientsSusceptible individualsAntibody specificityDiseaseReceptor specificitySerumHuman peptidome
2012
An RNA Profile Identifies Two Subsets of Multiple Sclerosis Patients Differing in Disease Activity
Ottoboni L, Keenan BT, Tamayo P, Kuchroo M, Mesirov JP, Buckle GJ, Khoury SJ, Hafler DA, Weiner HL, De Jager PL. An RNA Profile Identifies Two Subsets of Multiple Sclerosis Patients Differing in Disease Activity. Science Translational Medicine 2012, 4: 153ra131. PMID: 23019656, PMCID: PMC3753678, DOI: 10.1126/scitranslmed.3004186.Peer-Reviewed Original ResearchConceptsGlatiramer acetateDisease activityPatient populationFirst-line disease-modifying treatmentsMultiple sclerosis (MS) patient populationPeripheral blood mononuclear cellsMS patient populationDisease-modifying treatmentsMultiple sclerosis patientsBlood mononuclear cellsSubset of subjectsDisease courseSclerosis patientsMS subjectsMononuclear cellsInflammatory eventsTreatment responseUntreated subjectsAdditional groupHigh expressionTranscriptional signatureSubjectsRNA profilesTreatmentTranscriptional profiles
2007
Protective and therapeutic role for αB-crystallin in autoimmune demyelination
Ousman SS, Tomooka BH, van Noort JM, Wawrousek EF, O’Conner K, Hafler DA, Sobel RA, Robinson WH, Steinman L. Protective and therapeutic role for αB-crystallin in autoimmune demyelination. Nature 2007, 448: 474-479. PMID: 17568699, DOI: 10.1038/nature05935.Peer-Reviewed Original Research
2003
Myelin basic protein-reactive autoantibodies in the serum and cerebrospinal fluid of multiple sclerosis patients are characterized by low-affinity interactions
O'Connor KC, Chitnis T, Griffin DE, Piyasirisilp S, Bar-Or A, Khoury S, Wucherpfennig KW, Hafler DA. Myelin basic protein-reactive autoantibodies in the serum and cerebrospinal fluid of multiple sclerosis patients are characterized by low-affinity interactions. Journal Of Neuroimmunology 2003, 136: 140-148. PMID: 12620653, DOI: 10.1016/s0165-5728(03)00002-x.Peer-Reviewed Original ResearchConceptsMyelin basic proteinMultiple sclerosisCerebrospinal fluidSoluble myelin basic proteinSemple rabies vaccinePresence of autoantibodiesMultiple sclerosis patientsSera of patientsFraction of patientsAnti-MBP antibodiesHigh-affinity autoantibodiesBasic proteinMBP autoantibodiesRelevant autoantibodiesMS patientsSclerosis patientsAutoimmune diseasesHumoral responseRabies vaccineAutoantibodiesPatientsImmunodominant antigensSerumDiseaseSolid-phase assays
2000
Human and Murine CD4 T Cell Reactivity to a Complex Antigen: Recognition of the Synthetic Random Polypeptide Glatiramer Acetate
Duda P, Krieger J, Schmied M, Balentine C, Hafler D. Human and Murine CD4 T Cell Reactivity to a Complex Antigen: Recognition of the Synthetic Random Polypeptide Glatiramer Acetate. The Journal Of Immunology 2000, 165: 7300-7307. PMID: 11120865, DOI: 10.4049/jimmunol.165.12.7300.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsCD4-Positive T-LymphocytesCell Line, TransformedCell SeparationClone CellsDose-Response Relationship, ImmunologicFemaleGlatiramer AcetateHematopoietic Stem CellsHLA-DR AntigensHumansImmunizationImmunologic MemoryImmunomagnetic SeparationInfant, NewbornLeukocytes, MononuclearLymphocyte ActivationLymphocyte CountMiceMice, Inbred BALB CMice, Inbred C57BLMultiple Sclerosis, Relapsing-RemittingPeptidesSpleenTh1 CellsTh2 CellsConceptsT cell populationsHLA class II DRGlatiramer acetateT cell proliferationClass II DRII DRT cellsCD4 T cell reactivityGA-reactive T cellsHuman T cell proliferative responsesT cell precursor frequencyCell populationsSpecific human T cell clonesT cell proliferative responsesHuman T cell clonesMemory T cellsT cell reactivityMultiple sclerosis patientsRecent clinical findingsCell precursor frequencyCell proliferative responsesCell proliferationT cell clonesDose-dependent proliferationHealthy human adults
1999
Cross-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
Pulse Cyclophosphamide Plus Methylprednisolone Induces Myelin-Antigen-Specific IL-4-Secreting T Cells in Multiple Sclerosis Patients
Takashima H, Smith D, Fukaura H, Khoury S, Hafler D, Weiner H. Pulse Cyclophosphamide Plus Methylprednisolone Induces Myelin-Antigen-Specific IL-4-Secreting T Cells in Multiple Sclerosis Patients. Clinical Immunology 1998, 88: 28-34. PMID: 9683547, DOI: 10.1006/clin.1998.4558.Peer-Reviewed Original ResearchConceptsIL-4-secreting T cellsUntreated MS patientsProgressive MS patientsT cell linesMS patientsIL-4 secretionMyelin basic proteinT cellsMultiple sclerosisMyelin antigensTetanus toxoidTh1-type autoimmune diseaseShort-term T cell linesCell linesPulse cyclophosphamide therapyTh2-type responseIL-4 productionMultiple sclerosis patientsIFN-gamma productionProteolipid proteinImmune deviationPulse cyclophosphamideCyclophosphamide therapySclerosis patientsAutoimmune diseases
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
1995
A Review of T‐Cell Receptors in Multiple Sclerosis: Clonal Expansion and Persistence of Human T‐Cells Specific for an Immunodominant Myelin Basic Protein Peptidea
WUCHERPFENNIG K, HAFLER D. A Review of T‐Cell Receptors in Multiple Sclerosis: Clonal Expansion and Persistence of Human T‐Cells Specific for an Immunodominant Myelin Basic Protein Peptidea. Annals Of The New York Academy Of Sciences 1995, 756: 241-258. PMID: 7544075, DOI: 10.1111/j.1749-6632.1995.tb44522.x.Peer-Reviewed Original ResearchConceptsImmunodominant MBP peptidesT cell clonesMBP peptidesImmune responseNormal subjectsMBP-specific T cell clonesIndividual multiple sclerosis patientsTCR beta-chain usageMBP-specific T cellsTCR V beta chainsDR2 haplotypeSpecific T cell clonesBeta-chain usageT cell responsesAntigen-specific therapyMultiple sclerosis patientsSpecific T cellsDifferent T-cell linesT Cells SpecificIdentical TCR sequencesT cell receptorT cell linesAlpha-chain rearrangementMyelin antigensMS patientsReactivity of normal T-cell lines to MBP isolated from normal and multiple sclerosis white matter
McLaurin J, Hafler D, Antel J. Reactivity of normal T-cell lines to MBP isolated from normal and multiple sclerosis white matter. Journal Of The Neurological Sciences 1995, 128: 205-211. PMID: 7537795, DOI: 10.1016/0022-510x(94)00224-c.Peer-Reviewed Original ResearchConceptsT cell linesMyelin basic proteinMS white matterCentral nervous systemWhite matterMBP preparationsMS brainsPeripheral bloodRegion of MBPMultiple sclerosis white matterMBP-reactive T cell linesReactive T cell linesHuman T cell clonesT cell reactivityMultiple sclerosis patientsAutologous peripheral bloodNormal T-cell linesConcentration-response curvesT cell clonesAdult white matterHuman myelin basic proteinBasic proteinMS patientsSclerosis patientsMononuclear cellsTherapy for Multiple Sclerosis
Weiner H, Hohol M, Khoury S, Dawson D, Hafler D. Therapy for Multiple Sclerosis. Neurologic Clinics 1995, 13: 173-196. PMID: 7739502, DOI: 10.1016/s0733-8619(18)30066-5.Peer-Reviewed Original ResearchConceptsMultiple sclerosisCell-mediated autoimmune diseaseAccumulation of disabilityMultiple sclerosis patientsSymptomatic therapySclerosis patientsAutoimmune responseCentral nervous system myelinAutoimmune diseasesNonspecific modulationImmune systemSclerosisSystem myelinTherapyImmunotherapyPatientsDiseaseMyelin
1994
Increased frequency of interleukin 2-responsive T cells specific for myelin basic protein and proteolipid protein in peripheral blood and cerebrospinal fluid of patients with multiple sclerosis.
Zhang J, Markovic-Plese S, Lacet B, Raus J, Weiner HL, Hafler DA. Increased frequency of interleukin 2-responsive T cells specific for myelin basic protein and proteolipid protein in peripheral blood and cerebrospinal fluid of patients with multiple sclerosis. Journal Of Experimental Medicine 1994, 179: 973-984. PMID: 7509366, PMCID: PMC2191414, DOI: 10.1084/jem.179.3.973.Peer-Reviewed Original ResearchConceptsMyelin-reactive T cellsFrequency of MBPMBP-reactive T cell linesMBP-reactive T cellsMyelin basic proteinT cellsCerebrospinal fluidT cell linesMS patientsProteolipid proteinPLP-reactive T cellsNormal individualsFrequency of interleukinAutoreactive T cellsPathogenesis of MSMultiple sclerosis patientsIL-2-responsive cellsRIL-2 stimulationCentral nervous systemCell linesBasic proteinSclerosis patientsMultiple sclerosisPeripheral bloodPathogenic role
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-cell recognition of an immuno-dominant myelin basic protein epitope in multiple sclerosis
Ota K, Matsui M, Milford E, Mackin G, Weiner H, Hafler D. T-cell recognition of an immuno-dominant myelin basic protein epitope in multiple sclerosis. Nature 1990, 346: 183-187. PMID: 1694970, DOI: 10.1038/346183a0.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAntigen-Presenting CellsApoproteinsAutoantigensCells, CulturedEpitopesHLA-DR AntigensHumansIn Vitro TechniquesMajor Histocompatibility ComplexMolecular Sequence DataMultiple SclerosisMyelin Basic ProteinMyelin ProteinsMyelin Proteolipid ProteinPeptide FragmentsT-LymphocytesConceptsMultiple sclerosis patientsT cell linesMyelin basic proteinMultiple sclerosisSclerosis patientsT cellsVivo-activated T cellsShort-term T cell linesMyelin basic protein epitopeBasic proteinExperimental autoimmune encephalomyelitisDifferent T-cell linesCentral nervous systemMultiple sclerosis subjectsT cell recognitionT cell specificityAutoimmune encephalomyelitisImmune involvementAutoimmune diseasesPotential autoantigensNormal controlsNervous systemNeurological diseasesSclerosisPatients
1989
Decrease of suppressor inducer (cd4+ 2h4+) t cells in multiple sclerosis cerebrospinal fluid
Chofflon M, Weiner H, Morimoto C, Hafler D. Decrease of suppressor inducer (cd4+ 2h4+) t cells in multiple sclerosis cerebrospinal fluid. Annals Of Neurology 1989, 25: 494-499. PMID: 2528316, DOI: 10.1002/ana.410250512.Peer-Reviewed Original ResearchConceptsInducer T cellsSuppressor-inducer T cellsMultiple sclerosis patientsT cellsCerebrospinal fluidMultiple sclerosisPeripheral bloodSclerosis patientsInducer cellsInducer functionMultiple sclerosis cerebrospinal fluidHelper-inducer T cellsCentral nervous system compartmentHelper inducer functionHelper-inducer cellsLocal autoimmune processesSuppressor-inducer functionSuppressor-inducer cellsCentral nervous systemSamples of bloodFlow cytometric analysisHelper inducerAutoimmune processInflammatory disordersT lymphocytes
1988
Oligoclonal T lymphocytes in the cerebrospinal fluid of patients with multiple sclerosis.
Hafler DA, Duby AD, Lee SJ, Benjamin D, Seidman JG, Weiner HL. Oligoclonal T lymphocytes in the cerebrospinal fluid of patients with multiple sclerosis. Journal Of Experimental Medicine 1988, 167: 1313-1322. PMID: 3258624, PMCID: PMC2188923, DOI: 10.1084/jem.167.4.1313.Peer-Reviewed Original ResearchConceptsT cell clonesT cell populationsOligoclonal T-cell populationsTCR gene rearrangement patternsCerebrospinal fluidGene rearrangement patternsCell clonesT cellsRearrangement patternsChronic progressive multiple sclerosis patientsProgressive multiple sclerosis patientsCell populationsChronic progressive MSHerpes zoster meningoencephalitisOligoclonal T lymphocytesOligoclonal T cellsT cell responsesMultiple sclerosis patientsCentral nervous systemT cell receptor beta chainTCR gene rearrangementsIndividual T cellsProgressive MSGamma chain geneImmune compartment
1987
T Cells in Multiple Sclerosis and Inflammatory Central Nervous System Diseases
Hafler D, Weiner H. T Cells in Multiple Sclerosis and Inflammatory Central Nervous System Diseases. Immunological Reviews 1987, 100: 307-332. PMID: 3326824, DOI: 10.1111/j.1600-065x.1987.tb00537.x.Peer-Reviewed Original ResearchConceptsT cellsInflammatory responseCNS tissueInflammatory central nervous system diseasesProgressive multiple sclerosis patientsCentral nervous system diseaseClass II MHC antigensMonoclonal antibodiesT-cell receptor gene rearrangementsCSF T cellsOngoing inflammatory responseTotal T cellsInflammatory CNS diseaseMultiple sclerosis patientsAnti-measles antibodiesAntigen-presenting cellsChronic disease processesAntigen-specific cellsNervous system diseasesReceptor gene rearrangementsMurine monoclonal antibodiesSelective accumulationAlpha beta chainsCNS damageSclerosis patientsImmunosuppression in progressive multiple sclerosis with high dose intravenous cyclophosphamide and monoclonal antibodies.
Dawson DM, Carter JL, Hafler DA, Weiner HL. Immunosuppression in progressive multiple sclerosis with high dose intravenous cyclophosphamide and monoclonal antibodies. Nuova Rivista Di Neurologia 1987, 57: 88-91. PMID: 3039645.Peer-Reviewed Original ResearchConceptsProgressive multiple sclerosisMonoclonal antibody therapyMultiple sclerosisAntibody therapyChronic progressive multiple sclerosisHigh-dose intravenous cyclophosphamideMultiple sclerosis patientsForm of treatmentLong-term controlIntravenous cyclophosphamideSclerosis patientsClinical resultsSerious toxicityImmune parametersPilot trialCyclophosphamideNervous systemSclerosisTerm controlsPatientsMonoclonal antibodiesACTHOnly small numbersTherapyAdverse effects