2022
Basic principles of neuroimmunology
Yoshida TM, Wang A, Hafler DA. Basic principles of neuroimmunology. Seminars In Immunopathology 2022, 44: 685-695. PMID: 35732977, DOI: 10.1007/s00281-022-00951-7.Peer-Reviewed Original ResearchMeSH KeywordsCentral Nervous SystemCytokinesHumansLymphatic SystemNeuroimmunomodulationT-LymphocytesConceptsNeuro-immune interactionsCentral nervous systemImmune privilegeCerebrospinal fluidCNS-resident immune cellsImmune-derived cytokinesResident T cellsImmune cell infiltrationImmune-privileged organMeningeal lymphatic systemIntroduction of antigenImmune compartmentNeuroinflammatory diseasesNeurological functionCNS homeostasisCell infiltrationHarmful inflammationImmune cellsPeripheral organsT cellsImmune responseLeukocyte traffickingNervous systemImmune systemLymphatic system
2020
Transcriptomic and clonal characterization of T cells in the human central nervous system
Pappalardo JL, Zhang L, Pecsok MK, Perlman K, Zografou C, Raddassi K, Abulaban A, Krishnaswamy S, Antel J, van Dijk D, Hafler DA. Transcriptomic and clonal characterization of T cells in the human central nervous system. Science Immunology 2020, 5 PMID: 32948672, PMCID: PMC8567322, DOI: 10.1126/sciimmunol.abb8786.Peer-Reviewed Original ResearchMeSH KeywordsAdultCentral Nervous SystemHumansMultiple Sclerosis, Relapsing-RemittingT-LymphocytesTranscriptomeConceptsCentral nervous systemCSF of patientsT cellsCerebrospinal fluidMultiple sclerosisImmune surveillanceNervous systemCSF T cellsHuman central nervous systemHealthy human donorsT cell activationImmune dysfunctionNeuroinflammatory diseasesCytotoxic capacityHealthy donorsHealthy individualsCell activationHuman donorsTissue adaptationPatientsClonal characterizationExpression of genesCellsSurveillanceFurther characterization
2018
Enhanced astrocyte responses are driven by a genetic risk allele associated with multiple sclerosis
Ponath G, Lincoln MR, Levine-Ritterman M, Park C, Dahlawi S, Mubarak M, Sumida T, Airas L, Zhang S, Isitan C, Nguyen TD, Raine CS, Hafler DA, Pitt D. Enhanced astrocyte responses are driven by a genetic risk allele associated with multiple sclerosis. Nature Communications 2018, 9: 5337. PMID: 30559390, PMCID: PMC6297228, DOI: 10.1038/s41467-018-07785-8.Peer-Reviewed Original ResearchConceptsMultiple sclerosisAstrocyte responseRisk variantsLocal autoimmune inflammationPeripheral immune cellsCentral nervous system cellsPeripheral immune systemCultured human astrocytesNervous system cellsNF-κB signalingCNS accessDysfunctional lymphocytesAstroglial functionAutoimmune inflammationLymphocytic infiltrateLymphocyte recruitmentImmune cellsGenetic risk allelesGenetic risk variantsMS lesionsMS susceptibilityHuman astrocytesLesion sizeImmune systemSystem cellsSingle-cell RNA sequencing reveals microglia-like cells in cerebrospinal fluid during virologically suppressed HIV
Farhadian SF, Mehta SS, Zografou C, Robertson K, Price RW, Pappalardo J, Chiarella J, Hafler DA, Spudich SS. Single-cell RNA sequencing reveals microglia-like cells in cerebrospinal fluid during virologically suppressed HIV. JCI Insight 2018, 3: e121718. PMID: 30232286, PMCID: PMC6237230, DOI: 10.1172/jci.insight.121718.Peer-Reviewed Original ResearchConceptsCerebrospinal fluidHIV infectionImmune activationAntiretroviral therapyNeuronal injuryCentral nervous system immune activationLong-term suppressive antiretroviral therapySingle-cell RNA sequencingCNS immune activationDisease-associated microgliaSuppressive antiretroviral therapyImmune cell subsetsMicroglia-like cellsGene expression signaturesNeuronal damageNeuroinflammatory diseasesRNA sequencingCell subsetsCNS cellsNeurological conditionsRare subsetNeurocognitive impairmentMyeloid cellsCellular subsetsInfectionChapter 46 Multiple sclerosis
Cotsapas C, Mitrovic M, Hafler D. Chapter 46 Multiple sclerosis. Handbook Of Clinical Neurology 2018, 148: 723-730. PMID: 29478610, DOI: 10.1016/b978-0-444-64076-5.00046-6.Peer-Reviewed Original ResearchConceptsMultiple sclerosisCentral nervous system white matterNervous system white matterAutoimmune neurologic disordersDisease-modifying therapiesImmune function modulationSpecific immune subsetsCentral nervous systemGenetic variantsImmune subsetsNeurologic symptomsAutoimmune attackLeading causeNeurologic disordersNervous systemWhite matterCommon genetic variantsOverall riskSclerosisYoung adultsEnvironmental exposuresRiskSymptomsDiseasePatients
2012
Regulatory T cells in the central nervous system
Lowther DE, Hafler DA. Regulatory T cells in the central nervous system. Immunological Reviews 2012, 248: 156-169. PMID: 22725960, DOI: 10.1111/j.1600-065x.2012.01130.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCentral Nervous SystemCerebrovascular DisordersGliomaHumansMultiple SclerosisT-Lymphocytes, RegulatoryConceptsRegulatory T cellsTreg functionAutoimmune diseasesT cellsForkhead box protein 3Central nervous system diseaseBox protein 3Nervous system diseasesCentral nervous systemPotential therapeutic targetHuman immune systemTreg biologyPeripheral toleranceMultiple sclerosisCNS diseaseImmune surveillanceImmune responseSystem diseasesTherapeutic targetNervous systemImmune systemProtein 3DiseaseTregsCellsFingolimod for Multiple Sclerosis
Pelletier D, Hafler DA. Fingolimod for Multiple Sclerosis. New England Journal Of Medicine 2012, 366: 339-347. PMID: 22276823, DOI: 10.1056/nejmct1101691.Peer-Reviewed Original Research
2011
Related B cell clones populate the meninges and parenchyma of patients with multiple sclerosis
Lovato L, Willis SN, Rodig SJ, Caron T, Almendinger SE, Howell OW, Reynolds R, O’Connor K, Hafler DA. Related B cell clones populate the meninges and parenchyma of patients with multiple sclerosis. Brain 2011, 134: 534-541. PMID: 21216828, PMCID: PMC3030766, DOI: 10.1093/brain/awq350.Peer-Reviewed Original ResearchMeSH KeywordsB-LymphocytesCentral Nervous SystemClone CellsHumansImmunoglobulin Variable RegionMeningesMultiple SclerosisConceptsB cell clonesB cell aggregatesMultiple sclerosisCentral nervous systemParenchymal infiltratesCell clonesNervous systemMeningeal B cell aggregatesRelated B cell clonesProgressive multiple sclerosisB-cell infiltratesCerebral spinal fluidInflammatory plaquesCell infiltrateImmune compartmentParenchymal lesionsLymphoid tissueSclerosisSpinal fluidWhite matterPatientsGray matterBrain tissueInfiltratesMeninges
2010
A unique antibody gene signature is prevalent in the central nervous system of patients with multiple sclerosis
Ligocki AJ, Lovato L, Xiang D, Guidry P, Scheuermann RH, Willis SN, Almendinger S, Racke MK, Frohman EM, Hafler DA, O'Connor KC, Monson NL. A unique antibody gene signature is prevalent in the central nervous system of patients with multiple sclerosis. Journal Of Neuroimmunology 2010, 226: 192-193. PMID: 20655601, PMCID: PMC2937103, DOI: 10.1016/j.jneuroim.2010.06.016.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodiesB-LymphocytesCentral Nervous SystemFemaleHumansMaleMiddle AgedMultiple SclerosisReceptors, Antigen, B-CellConceptsMultiple sclerosisB cellsGene signatureMS brain tissueCSF of patientsCNS tissue samplesEnriched B cellsCentral nervous systemB cell receptorMS brainsTissue injuryNervous systemBrain tissueCell receptorTissue samplesSclerosisPatientsCSFUnique accumulationCellsSomatic hypermutationInjuryBrainReceptors
2009
T-Cells in Multiple Sclerosis
Severson C, Hafler DA. T-Cells in Multiple Sclerosis. 2009, 51: 1-24. PMID: 19582415, DOI: 10.1007/400_2009_12.Peer-Reviewed Original ResearchConceptsMultiple sclerosisT cellsMultifocal demyelinating diseaseMultiple cell subtypesRegulatory T cellsT cell subsetsT cell functionCentral nervous systemRational therapeutic strategiesT cell activationDemyelinating diseaseMS pathogenesisMS pathophysiologyCell subsetsAdaptive immunityEffective treatmentTherapeutic strategiesNervous systemCell activationCell subtypesEvidence implicateSpecific toleranceFunctional defectsIntrinsic cellsCell function
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 models
2005
Antibodies from Inflamed Central Nervous System Tissue Recognize Myelin Oligodendrocyte Glycoprotein
O’Connor K, Appel H, Bregoli L, Call ME, Catz I, Chan JA, Moore NH, Warren KG, Wong SJ, Hafler DA, Wucherpfennig KW. Antibodies from Inflamed Central Nervous System Tissue Recognize Myelin Oligodendrocyte Glycoprotein. The Journal Of Immunology 2005, 175: 1974-1982. PMID: 16034142, PMCID: PMC4515951, DOI: 10.4049/jimmunol.175.3.1974.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAutoantibodiesBinding Sites, AntibodyCentral Nervous SystemDemyelinating Autoimmune Diseases, CNSFemaleFluoroimmunoassayHumansMaleMolecular Sequence DataMultiple SclerosisMyelin ProteinsMyelin-Associated GlycoproteinMyelin-Oligodendrocyte GlycoproteinRadioimmunoassaySolutionsConceptsMyelin oligodendrocyte glycoproteinMultiple sclerosisCNS diseaseOligodendrocyte glycoproteinCNS tissueChronic inflammatory CNS diseasesAutoantibody-mediated pathologyInflammatory CNS diseasesCentral nervous system tissueInflammatory CNS diseaseCases of encephalitisHigh-affinity autoantibodiesCases of subacuteNervous system tissueCNS parenchymaMOG autoantibodiesMS patientsOligodendrocyte lossMOG-AbCNS diseasesAutoantibodiesCerebrospinal fluidMOG proteinPostmortem casesControl tissuesMultiple sclerosis
Hafler DA, Slavik JM, Anderson DE, O'Connor KC, De Jager P, Baecher‐Allan C. Multiple sclerosis. Immunological Reviews 2005, 204: 208-231. PMID: 15790361, DOI: 10.1111/j.0105-2896.2005.00240.x.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAnimalsAutoantibodiesCentral Nervous SystemGenetic VariationHumansImmunosuppression TherapyMultiple SclerosisT-LymphocytesConceptsMultiple sclerosisT cellsB cellsImmunopathology of MSCentral nervous system white matterNervous system white matterRegulatory T cellsHallmark of inflammationImmunosuppressive therapyAutoimmune processImmunomodulatory therapeuticsAnimal modelsMS researchWhite matterDisease pathologyClonal expansionDiseaseMajor histocompatibility complex (MHC) genesMolecular pathologyRNA expressionSclerosisInflammationTherapyPathologyComplex genetic diseasesHigh Incidence of Spontaneous Disease in an HLA-DR15 and TCR Transgenic Multiple Sclerosis Model
Ellmerich S, Mycko M, Takacs K, Waldner H, Wahid FN, Boyton RJ, King RH, Smith PA, Amor S, Herlihy AH, Hewitt RE, Jutton M, Price DA, Hafler DA, Kuchroo VK, Altmann DM. High Incidence of Spontaneous Disease in an HLA-DR15 and TCR Transgenic Multiple Sclerosis Model. The Journal Of Immunology 2005, 174: 1938-1946. PMID: 15699121, DOI: 10.4049/jimmunol.174.4.1938.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigen PresentationCell MovementCentral Nervous SystemDisease Models, AnimalDisease ProgressionDNA-Binding ProteinsEpitopes, T-LymphocyteHLA-DR AntigensHLA-DR Serological SubtypesMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicMultiple SclerosisMyelin Basic ProteinParalysisPeptide FragmentsReceptors, Antigen, T-Cell, alpha-betaT-Lymphocyte SubsetsConceptsT cell responsesHLA-DR15Multiple sclerosisDeterminant spreadSpontaneous diseaseCell responsesCD4 T cell recognitionCNS tissue damageHuman multiple sclerosisMultiple sclerosis modelT cell reactivityExperimental allergic encephalomyelitisMyelin oligodendrocyte glycoproteinT cell recognitionMyelin basic proteinAllergic encephalomyelitisMyelin epitopesPeptide immunotherapyAxonal degenerationCell reactivityOligodendrocyte glycoproteinPathogenic roleT cellsHigh incidenceTransgenic mice
1989
Immunoregulation in multiple sclerosis
Hafler DA, Brod SA, Weiner HL. Immunoregulation in multiple sclerosis. Research In Immunology 1989, 140: 233-239. PMID: 2525796, DOI: 10.1016/0923-2494(89)90093-x.Peer-Reviewed Original Research
1984
Altered blood T-cell subsets in patients with multiple sclerosis
Weiner H, Hafler D, Fallis R, Johnson D, Ault K, Hauser S. Altered blood T-cell subsets in patients with multiple sclerosis. Journal Of Neuroimmunology 1984, 6: 115-121. PMID: 6373819, DOI: 10.1016/0165-5728(84)90032-8.Peer-Reviewed Original ResearchConceptsT cell subsetsMultiple sclerosisBlood T cell subsetsChronic progressive patientsActive multiple sclerosisStage of illnessSpontaneous immunoglobulin productionCentral nervous systemImmunoregulatory abnormalitiesT8 ratioActive diseaseDisease activityProgressive patientsAcute patientsPeripheral bloodImmunoglobulin productionImmune functionPatientsNervous systemSclerosisSpinal fluidDiagnostic testsAbnormalitiesVariety of protocolsPleocytosis