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
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
2009
The role of the CD58 locus in multiple sclerosis
De Jager PL, Baecher-Allan C, Maier LM, Arthur AT, Ottoboni L, Barcellos L, McCauley JL, Sawcer S, Goris A, Saarela J, Yelensky R, Price A, Leppa V, Patterson N, de Bakker PI, Tran D, Aubin C, Pobywajlo S, Rossin E, Hu X, Ashley CW, Choy E, Rioux JD, Pericak-Vance MA, Ivinson A, Booth DR, Stewart GJ, Palotie A, Peltonen L, Dubois B, Haines JL, Weiner HL, Compston A, Hauser SL, Daly MJ, Reich D, Oksenberg JR, Hafler DA. The role of the CD58 locus in multiple sclerosis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 106: 5264-5269. PMID: 19237575, PMCID: PMC2664005, DOI: 10.1073/pnas.0813310106.Peer-Reviewed Original ResearchConceptsMultiple sclerosisMS subjectsMononuclear cellsCD58 expressionProtective effectMRNA expressionPeripheral blood mononuclear cellsRegulatory T cellsBlood mononuclear cellsTranscription factor Foxp3Dose-dependent increaseCentral nervous systemLymphoblastic cell linesClinical remissionAxonal lossControl subjectsInflammatory diseasesFactor Foxp3T cellsWhole-genome association scansLFA-3Nervous systemProtective allelesPotential mechanismsSclerosis
2008
Concurrent detection of secreted products from human lymphocytes by microengraving: Cytokines and antigen-reactive antibodies
Bradshaw EM, Kent SC, Tripuraneni V, Orban T, Ploegh HL, Hafler DA, Love JC. Concurrent detection of secreted products from human lymphocytes by microengraving: Cytokines and antigen-reactive antibodies. Clinical Immunology 2008, 129: 10-18. PMID: 18675591, PMCID: PMC2577144, DOI: 10.1016/j.clim.2008.06.009.Peer-Reviewed Original ResearchConceptsHuman peripheral blood mononuclear cellsPeripheral blood mononuclear cellsType 1 diabetic subjectsAntigen-reactive antibodiesBlood mononuclear cellsAntigen-specific antibodiesAnti-insulin antibodiesCell surface determinantsDiabetic subjectsIL-6Mononuclear cellsPositive titersIgG isotypeB cellsHuman lymphocytesSurface determinantsCytokinesAntibodiesClinical samplesHematopoietic cellsRare populationCellsMarkersHuman cellsLymphocytes
2006
Sa.128. Comparison of Two Methods to Isolate Mononuclear Cells from Peripheral Blood On Viability and Function of Freshly and Cryopreserved PBMCS
Raddassi K, Estevam J, Bourcier K, Gisler T, Hafler D, Seyfert-Margolis V. Sa.128. Comparison of Two Methods to Isolate Mononuclear Cells from Peripheral Blood On Viability and Function of Freshly and Cryopreserved PBMCS. Clinical Immunology 2006, 119: s150-s151. DOI: 10.1016/j.clim.2006.04.360.Peer-Reviewed Original Research
2004
T Cell Ig- and Mucin-Domain-Containing Molecule-3 (TIM-3) and TIM-1 Molecules Are Differentially Expressed on Human Th1 and Th2 Cells and in Cerebrospinal Fluid-Derived Mononuclear Cells in Multiple Sclerosis
Khademi M, Illés Z, Gielen AW, Marta M, Takazawa N, Baecher-Allan C, Brundin L, Hannerz J, Martin C, Harris RA, Hafler DA, Kuchroo VK, Olsson T, Piehl F, Wallström E. T Cell Ig- and Mucin-Domain-Containing Molecule-3 (TIM-3) and TIM-1 Molecules Are Differentially Expressed on Human Th1 and Th2 Cells and in Cerebrospinal Fluid-Derived Mononuclear Cells in Multiple Sclerosis. The Journal Of Immunology 2004, 172: 7169-7176. PMID: 15153541, DOI: 10.4049/jimmunol.172.11.7169.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedCell LineCell PolarityCerebrospinal FluidCytokinesFemaleGene Expression RegulationHepatitis A Virus Cellular Receptor 1Hepatitis A Virus Cellular Receptor 2HumansMaleMembrane GlycoproteinsMembrane ProteinsMiddle AgedMultiple SclerosisReceptors, VirusRNA, MessengerTh1 CellsTh2 CellsConceptsCerebrospinal fluid mononuclear cellsFluid mononuclear cellsT cell IgMononuclear cellsTim-3Multiple sclerosisTh2 cellsTIM-1Human Th1TIM moleculesMucin-domain-containing moleculesTim-3 mRNA levelsTh2-mediated diseasesHigh expressionExperimental autoimmune encephalomyelitisHuman autoimmune diseasesTIM-1 expressionIFN-gamma mRNAReal-time RT-PCRTim-1 polymorphismsTh1 cell clonesHigher mRNA expressionAirway hyperreactivityClinical remissionAutoimmune encephalomyelitis
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
1999
Noncanonical Vα24JαQ T cells with conservative α chain CDR3 region amino acid substitutions are restricted by CD1d
Kent S, Hafler D, Strominger J, Wilson S. Noncanonical Vα24JαQ T cells with conservative α chain CDR3 region amino acid substitutions are restricted by CD1d. Human Immunology 1999, 60: 1080-1089. PMID: 10600006, DOI: 10.1016/s0198-8859(99)00109-3.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAntigens, CD1Antigens, CD1dBase SequenceClone CellsComplementarity Determining RegionsConserved SequenceDNAGene Rearrangement, alpha-Chain T-Cell Antigen ReceptorHumansImmunoglobulin Variable RegionImmunophenotypingKiller Cells, NaturalReceptors, Antigen, T-Cell, alpha-betaT-Lymphocyte SubsetsConceptsT cell receptorT cellsCD1d restrictionPeripheral blood mononuclear cellsBlood mononuclear cellsAmino acid substitutionsAlpha chainSingle amino acid substitutionHuman CD161Total CD4Mononuclear cellsInterleukin-4Surface phenotypeRestriction elementsCD4Acid substitutionsCD1dCDR3 residuesJ rearrangementsJ junctionsVariant clonesChain transcriptsCellsJalpha18Valpha24
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
1996
Induction of anergy in CD8 T cells by B cell presentation of antigen.
Höllsberg P, Batra V, Dressel A, Hafler DA. Induction of anergy in CD8 T cells by B cell presentation of antigen. The Journal Of Immunology 1996, 157: 5269-76. PMID: 8955172, DOI: 10.4049/jimmunol.157.12.5269.Peer-Reviewed Original ResearchMeSH KeywordsAntigen-Presenting CellsB7-1 AntigenB-LymphocytesCD40 LigandCD8-Positive T-LymphocytesCell LineClonal AnergyCytotoxicity, ImmunologicGene ExpressionHumansImmunologic MemoryInterleukin-2Lymphocyte ActivationMembrane GlycoproteinsReceptors, Antigen, T-CellSignal TransductionTranscription, GeneticConceptsCD8 T cellsT cell clonesInduction of anergyT cellsB cellsMononuclear cellsB7-1Cell clonesAg stimulationAnergic CD8 T cellsPeptide-pulsed B cellsPeptide-pulsed target cellsCD4 T-cell clonesCD8 T cell clonesSecondary Ag challengeExogenous IL-2B7-2 costimulationB cell presentationT cell anergyIL-2 secretionNormal proliferative responseIL-2 mRNA transcriptionT cell stimulationEarly tyrosine phosphorylationAdequate costimulation
1995
Reactivity 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 cells
1992
Characterization 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
1989
Inflammatory cerebrospinal fluid t cells have activation requirements characteristic of cd4+cd45ra‐ t cells
Chofflon M, González V, Weiner H, Hafler D. Inflammatory cerebrospinal fluid t cells have activation requirements characteristic of cd4+cd45ra‐ t cells. European Journal Of Immunology 1989, 19: 1791-1795. PMID: 2479560, DOI: 10.1002/eji.1830191005.Peer-Reviewed Original ResearchConceptsCSF T cellsPhorbol myristate acetateMononuclear cellsCSF mononuclear cellsT cellsCerebrospinal fluidCerebrospinal fluid T cellsCSF of subjectsProtein kinase CCD3/T cell receptor complexInflammatory brain diseasesBlood mononuclear cellsT cell populationsSorted T cellsInterleukin-2 receptorInterleukin-2 secretionCD2 activation pathwayT cell receptor complexKinase CInflammatory compartmentMultiple sclerosisCNS diseaseCell receptor complexImmune responseNormal subjects
1988
Loss of functional suppression is linked to decreases in circulating suppressor inducer (CD4 + 2H4 +) T Cells in multiple sclerosis
Chofflon M, Weiner H, Morimoto C, Hafler D. Loss of functional suppression is linked to decreases in circulating suppressor inducer (CD4 + 2H4 +) T Cells in multiple sclerosis. Annals Of Neurology 1988, 24: 185-191. PMID: 2972249, DOI: 10.1002/ana.410240203.Peer-Reviewed Original ResearchConceptsSuppressor-inducer T cellsProgressive multiple sclerosisInducer T cellsSuppressor T cellsMultiple sclerosisT cellsFunctional suppressionTwo-color immunofluorescenceImmunoregulatory abnormalitiesImmunological findingsIgG synthesisMononuclear cellsPokeweed mitogenImmunoglobulin synthesisNormal subjectsSclerosisCD4Neurological diseasesAMLRPatientsTwo-stage assaySuppressor functionSignificant correlationPresent studyCells