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 ResearchMeSH KeywordsAntigens, CD20CD8-Positive T-LymphocytesFlow CytometryHumansLeukocytes, MononuclearMultiple SclerosisRecurrenceConceptsEarly 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
2015
Sodium chloride inhibits the suppressive function of FOXP3+ regulatory T cells
Hernandez AL, Kitz A, Wu C, Lowther DE, Rodriguez DM, Vudattu N, Deng S, Herold KC, Kuchroo VK, Kleinewietfeld M, Hafler DA. Sodium chloride inhibits the suppressive function of FOXP3+ regulatory T cells. Journal Of Clinical Investigation 2015, 125: 4212-4222. PMID: 26524592, PMCID: PMC4639983, DOI: 10.1172/jci81151.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsAntibodies, NeutralizingAutoimmunityCD4-Positive T-LymphocytesCells, CulturedCoculture TechniquesColitisCytokinesForkhead Transcription FactorsGene Expression ProfilingGenes, ReporterGraft vs Host DiseaseHeterograftsHumansImmediate-Early ProteinsInflammationInterferon-gammaLeukocytes, MononuclearMaleMiceProtein Serine-Threonine KinasesRNA InterferenceRNA, Small InterferingSodium ChlorideSodium Chloride, DietaryT-Lymphocytes, RegulatoryConceptsHigh-salt dietTreg functionIFNγ secretionCD4 effector cellsHuman Treg functionRegulatory T cellsAdoptive transfer modelAnti-IFNγ antibodyHost disease modelType 1 diabetesInduction of proinflammatoryTreg pathwayExperimental colitisXenogeneic graftEffector cellsMultiple sclerosisProinflammatory responseT cellsTregsMurine modelSuppressive activitySuppressive functionSerum/glucocorticoid-regulated kinaseAutoimmunityGlucocorticoid-regulated kinase
2014
TLR7 induces anergy in human CD4+ T cells
Dominguez-Villar M, Gautron AS, de Marcken M, Keller MJ, Hafler DA. TLR7 induces anergy in human CD4+ T cells. Nature Immunology 2014, 16: 118-128. PMID: 25401424, PMCID: PMC4413902, DOI: 10.1038/ni.3036.Peer-Reviewed Original Research
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 ResearchMeSH KeywordsAntibodiesCytokinesHumansImmunoassayInterferon-gammaInterleukin-6Leukocytes, MononuclearTissue Array AnalysisConceptsHuman 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
2003
CD4+CD25+ Regulatory Cells from Human Peripheral Blood Express Very High Levels of CD25 Ex Vivo
Baecher‐Allan C, Brown JA, Freeman GJ, Hafler DA. CD4+CD25+ Regulatory Cells from Human Peripheral Blood Express Very High Levels of CD25 Ex Vivo. Novartis Foundation Symposia 2003, 252: 67-91. PMID: 14609213, DOI: 10.1002/0470871628.ch6.Peer-Reviewed Original ResearchConceptsT cellsRegulatory cellsPD-1/PD-L1 interactionLigand PD-L1Responder T cellsPD-L1 interactionContact-dependent mannerCo-culture assaysCTLA4 blockadeRegulatory populationPD-1PD-L1HLA-DRMultiple surface antigensCytokine secretionCD45RA expressionSurface antigenEx vivoLevel of expressionModest inductionSuppressive characteristicsFunctional activityHigh levelsCD25CD45RO
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 adultsA novel population of B7‐1+ T cells producing intracellular IL‐4 is decreased in patients with multiple sclerosis
Kipp B, Bar‐Or A, Gausling R, Oliveira E, Fruhan S, Stuart W, Hafler D. A novel population of B7‐1+ T cells producing intracellular IL‐4 is decreased in patients with multiple sclerosis. European Journal Of Immunology 2000, 30: 2092-2100. PMID: 10940899, DOI: 10.1002/1521-4141(200007)30:7<2092::aid-immu2092>3.0.co;2-7.Peer-Reviewed Original ResearchConceptsT cell receptorIntracellular IL-4Multiple sclerosisT cellsB7-1IL-4Autoimmune diseasesTNF-alphaIFN-gammaIL-4-producing T cellsLittle IL-4Immunoregulatory T cellsIL-4 productionIntracellular IFN-gammaT cell populationsLittle IFN-gammaNovel populationDiverse TCR repertoireMHC class IIHuman T cellsShort-term cultureCell surface moleculesTCR repertoireNormal subjectsPatientsGlatiramer 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