2013
Sodium chloride drives autoimmune disease by the induction of pathogenic TH17 cells
Kleinewietfeld M, Manzel A, Titze J, Kvakan H, Yosef N, Linker RA, Muller DN, Hafler DA. Sodium chloride drives autoimmune disease by the induction of pathogenic TH17 cells. Nature 2013, 496: 518-522. PMID: 23467095, PMCID: PMC3746493, DOI: 10.1038/nature11868.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCells, CulturedEncephalomyelitis, Autoimmune, ExperimentalGene SilencingGranulocyte-Macrophage Colony-Stimulating FactorHumansImmediate-Early ProteinsInterleukin-2MAP Kinase Signaling SystemMiceMice, Inbred C57BLP38 Mitogen-Activated Protein KinasesPhenotypeProtein Serine-Threonine KinasesSodium Chloride, DietaryTh17 CellsTranscription FactorsTumor Necrosis Factor-alpha
2012
High salt induces pathogenic Th17 cells and exacerbates autoimmune diseases (60.13)
Kleinewietfeld M, Manzel A, Wu C, Titze J, Kuchroo V, Linker R, Muller D, Hafler D. High salt induces pathogenic Th17 cells and exacerbates autoimmune diseases (60.13). The Journal Of Immunology 2012, 188: 60.13-60.13. DOI: 10.4049/jimmunol.188.supp.60.13.Peer-Reviewed Original ResearchPathogenic Th17 cellsExperimental autoimmune encephalomyelitisEnvironmental risk factorsTh17 cellsAutoimmune diseasesRisk factorsMultiple sclerosisHigh-salt dietHelper T cellsGenetic risk factorsExacerbated inductionAutoimmune encephalomyelitisSalt dietSalt intakeCardiovascular diseaseT cellsSun exposureSevere formDiseaseGenetic factorsDietCertain pathogensInduction of murineInductionPivotal role
2007
Self-antigen tetramers discriminate between myelin autoantibodies to native or denatured protein
O'Connor KC, McLaughlin KA, De Jager PL, Chitnis T, Bettelli E, Xu C, Robinson WH, Cherry SV, Bar-Or A, Banwell B, Fukaura H, Fukazawa T, Tenembaum S, Wong SJ, Tavakoli NP, Idrissova Z, Viglietta V, Rostasy K, Pohl D, Dale RC, Freedman M, Steinman L, Buckle GJ, Kuchroo VK, Hafler DA, Wucherpfennig KW. Self-antigen tetramers discriminate between myelin autoantibodies to native or denatured protein. Nature Medicine 2007, 13: 211-217. PMID: 17237795, PMCID: PMC3429369, DOI: 10.1038/nm1488.Peer-Reviewed Original ResearchConceptsAcute disseminated encephalomyelitisMyelin oligodendrocyte glycoproteinMultiple sclerosisFluorescent-activated cell sortingRole of autoantibodiesExperimental autoimmune encephalomyelitisConformation-independent antibodiesDiscrimination of antibodiesMOG-specific autoantibodiesDisseminated encephalomyelitisMOG peptidesAutoimmune encephalomyelitisOligodendrocyte glycoproteinAutoantibody detectionTarget antigenAutoantibodiesMS casesELISA methodWestern blottingRadioimmunoassayAntibodiesEncephalomyelitisAntigen domainSensitive assayConformation-sensitive antibodies
2004
Cross-Reactive TCR Responses to Self Antigens Presented by Different MHC Class II Molecules
Mycko MP, Waldner H, Anderson DE, Bourcier KD, Wucherpfennig KW, Kuchroo VK, Hafler DA. Cross-Reactive TCR Responses to Self Antigens Presented by Different MHC Class II Molecules. The Journal Of Immunology 2004, 173: 1689-1698. PMID: 15265898, DOI: 10.4049/jimmunol.173.3.1689.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAmino Acid SubstitutionAnimalsAntigen PresentationAutoantigensCD4 AntigensCross ReactionsEncephalomyelitis, Autoimmune, ExperimentalHLA-DR alpha-ChainsHLA-DR AntigensHLA-DRB1 ChainsHumansHybridomasL CellsLymphocyte ActivationMembrane ProteinsMiceMolecular Sequence DataMultiple Sclerosis, Relapsing-RemittingMyelin Basic ProteinPeptide FragmentsPhosphorylationProtein Processing, Post-TranslationalReceptors, Antigen, T-CellReceptors, Antigen, T-Cell, alpha-betaT-Lymphocyte SubsetsTransfectionConceptsAutoreactive T cellsMHC class II moleculesClass II moleculesT cellsSpontaneous experimental autoimmune encephalomyelitisRelapsing-remitting multiple sclerosisDifferent MHC class II moleculesExperimental autoimmune encephalomyelitisAltered peptide ligandTh cell clonesT cell hybridomasMyelin basic proteinAutoimmune encephalomyelitisMultiple sclerosisSelf antigensCD4 coreceptorRestriction elementsHealthy individualsDiseased patientsHuman TCRPatientsTCR responsesCell clonesCell hybridomasPeptide ligandsT 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
1994
Regulatory T Cell Clones Induced by Oral Tolerance: Suppression of Autoimmune Encephalomyelitis
Chen Y, Kuchroo V, Inobe J, Hafler D, Weiner H. Regulatory T Cell Clones Induced by Oral Tolerance: Suppression of Autoimmune Encephalomyelitis. Science 1994, 265: 1237-1240. PMID: 7520605, DOI: 10.1126/science.7520605.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAmino Acid SequenceAnimalsCD4-Positive T-LymphocytesClone CellsEncephalomyelitis, Autoimmune, ExperimentalEpitopesImmune ToleranceInterleukin-10Interleukin-4Lymph NodesMajor Histocompatibility ComplexMesenteryMiceMolecular Sequence DataMyelin Basic ProteinMyelin ProteinsMyelin Proteolipid ProteinReceptors, Antigen, T-CellTransforming Growth Factor betaConceptsExperimental autoimmune encephalomyelitisMyelin basic proteinT cell clonesAutoimmune encephalomyelitisT cell receptor usageCell-mediated autoimmune diseaseMajor histocompatibility complex restrictionRegulatory T-cell clonesCell clonesMesenteric lymph nodesTh2-like clonesOral antigenOral toleranceEncephalitogenic CD4Lymph nodesPeripheral toleranceInterleukin-10Multiple sclerosisSJL miceAutoimmune diseasesOral administrationT cellsImmune responseInterleukin-4Animal modelsT cell receptor (TCR) usage determines disease susceptibility in experimental autoimmune encephalomyelitis: studies with TCR V beta 8.2 transgenic mice.
Kuchroo VK, Collins M, al-Sabbagh A, Sobel RA, Whitters MJ, Zamvil SS, Dorf ME, Hafler DA, Seidman JG, Weiner HL. T cell receptor (TCR) usage determines disease susceptibility in experimental autoimmune encephalomyelitis: studies with TCR V beta 8.2 transgenic mice. Journal Of Experimental Medicine 1994, 179: 1659-1664. PMID: 8163944, PMCID: PMC2191471, DOI: 10.1084/jem.179.5.1659.Peer-Reviewed Original ResearchConceptsExperimental allergic encephalomyelitisMyelin basic proteinAutoimmune diseasesEncephalitogenic epitopeTCR repertoireTCR VProteolipid proteinTransgenic miceT cell receptor usageDiverse T cell repertoireT cell receptor repertoireExperimental autoimmune encephalomyelitisAutoreactive T cellsCell receptor repertoireT cell repertoireT cell clonesAutoimmune encephalomyelitisAllergic encephalomyelitisSJL miceT cellsCell repertoirePLP epitopesReceptor usageReceptor repertoireImmunizationOral Tolerance: Immunologic Mechanisms and Treatment of Animal and Human Organ-Specific Autoimmune Diseases by Oral Administration of Autoantigens
Weiner HL, Friedman A, Miller A, Khoury SJ, al-Sabbagh A, Santos L, Sayegh M, Nussenblatt RB, Trentham DE, Hafler DA. Oral Tolerance: Immunologic Mechanisms and Treatment of Animal and Human Organ-Specific Autoimmune Diseases by Oral Administration of Autoantigens. Annual Review Of Immunology 1994, 12: 809-837. PMID: 8011298, DOI: 10.1146/annurev.iy.12.040194.004113.Peer-Reviewed Original ResearchConceptsOrgan-specific autoimmune diseasesExperimental autoimmune encephalomyelitisAntigen-specific fashionOral toleranceRegulatory cellsSuppressive cytokinesAutoimmune diseasesClonal anergyHuman organ-specific autoimmune diseasesGut-associated lymphoid tissueAntigen-nonspecific fashionExperimental autoimmune modelsTh2-type responsePositive clinical effectsProlong graft survivalPeripheral immune toleranceT cell autoreactivityInitial clinical trialsAntigen-induced toleranceActive suppressionOral tolerizationSuppress alloreactivityGraft survivalNOD miceAutoimmune encephalomyelitis
1991
Tolerance and suppressor mechanisms in experimental autoimmune encephalomyelitis: implications for immunotherapy of human autoimmune diseases
Miller A, Hafler D, Weiner H. Tolerance and suppressor mechanisms in experimental autoimmune encephalomyelitis: implications for immunotherapy of human autoimmune diseases. The FASEB Journal 1991, 5: 2560-2566. PMID: 1868980, DOI: 10.1096/fasebj.5.11.1868980.Peer-Reviewed Original ResearchConceptsExperimental autoimmune encephalomyelitisAutoimmune encephalomyelitisAutoimmune diseasesAnimal model experimental autoimmune encephalomyelitisModel experimental autoimmune encephalomyelitisHuman disease multiple sclerosisSpecific immune interventionAutoimmune T cellsHuman autoimmune diseasesNormal immune systemDisease multiple sclerosisMajor histocompatibility complexImmunospecific therapyTrimolecular complexImmune interventionSelective immunotherapyMultiple sclerosisT cellsImmune functionNonspecific modulationImmune systemAntigen recognitionHistocompatibility complexSuppressor mechanismDiseaseSuppression of experimental autoimmune encephalomyelitis by oral administration of myelin antigens: IV. Suppression of chronic relapsing disease in the lewis rat and strain 13 guinea pig
Brod S, al‐Sabbagh A, Sobel R, Hafler D, Weiner H. Suppression of experimental autoimmune encephalomyelitis by oral administration of myelin antigens: IV. Suppression of chronic relapsing disease in the lewis rat and strain 13 guinea pig. Annals Of Neurology 1991, 29: 615-622. PMID: 1716432, DOI: 10.1002/ana.410290608.Peer-Reviewed Original ResearchConceptsExperimental autoimmune encephalomyelitisAutoimmune encephalomyelitisMyelin antigensGuinea pig myelinOral administrationCentral nervous systemLewis ratsMyelin basic proteinAntigen-specific peripheral immune toleranceGuinea pigsMonophasic experimental autoimmune encephalomyelitisDelayed-type hypersensitivity responseGuinea pig myelin basic proteinHuman demyelinating disordersOngoing immune responsePig myelin basic proteinComplete Freund's adjuvantPeripheral immune toleranceExacerbation of diseaseHuman autoimmune diseasesBasic proteinClinical relapseDemyelinating disorderOral toleranceCNS demyelination
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