2014
Cell-selective knockout and 3D confocal image analysis reveals separate roles for astrocyte-and endothelial-derived CCL2 in neuroinflammation
Paul D, Ge S, Lemire Y, Jellison ER, Serwanski DR, Ruddle NH, Pachter JS. Cell-selective knockout and 3D confocal image analysis reveals separate roles for astrocyte-and endothelial-derived CCL2 in neuroinflammation. Journal Of Neuroinflammation 2014, 11: 10. PMID: 24444311, PMCID: PMC3906899, DOI: 10.1186/1742-2094-11-10.Peer-Reviewed Original ResearchConceptsExperimental autoimmune encephalomyelitisBlood-brain barrierCentral nervous systemBrain microvascular endothelial cellsKO miceEarly experimental autoimmune encephalomyelitisMyelin oligodendrocyte glycoprotein peptideEndothelial cellsNormal central nervous systemReduced EAE severityClinical disease progressionIFN-γ productionT cell proliferationWild-type miceMicrovascular endothelial cellsCCL2 immunoreactivityEAE severityImmunofluorescence confocal microscopyBBB damageEAE modelAutoimmune encephalomyelitisIL-17Neuroinflammatory conditionsNeuroinflammatory diseasesWT mice
2013
The development of tertiary lymphoid organs in the central nervous system facilitates determinant spreading of the MP4-specific T cell response (P4164)
Kuerten S, Schickel A, Kerkloh C, Recks M, Addicks K, Ruddle N, Lehmann P. The development of tertiary lymphoid organs in the central nervous system facilitates determinant spreading of the MP4-specific T cell response (P4164). The Journal Of Immunology 2013, 190: 172.9-172.9. DOI: 10.4049/jimmunol.190.supp.172.9.Peer-Reviewed Original ResearchTertiary lymphoid organsT cell responsesCentral nervous systemExperimental autoimmune encephalomyelitisMyelin oligodendrocyte glycoproteinMultiple sclerosisCell responsesLymphoid organsNervous systemFormation of TLOsAntigen-specific T cell responsesSecondary progressive multiple sclerosisHuman autoimmune disease multiple sclerosisAutoimmune disease multiple sclerosisT cell compartmentalizationB cell aggregatesChronic disease stageDisease multiple sclerosisSevere clinical diseaseHigh endothelial venulesGerminal center formationMyelin basic proteinAutoimmune encephalomyelitisCNS autoimmunityCortical pathology
2012
Tertiary lymphoid organ development coincides with determinant spreading of the myelin-specific T cell response
Kuerten S, Schickel A, Kerkloh C, Recks MS, Addicks K, Ruddle NH, Lehmann PV. Tertiary lymphoid organ development coincides with determinant spreading of the myelin-specific T cell response. Acta Neuropathologica 2012, 124: 861-873. PMID: 22842876, DOI: 10.1007/s00401-012-1023-3.Peer-Reviewed Original ResearchConceptsTertiary lymphoid organsExperimental autoimmune encephalomyelitisMyelin-specific T cell responseCentral nervous systemB cell aggregatesT cell responsesMultiple sclerosisB cell aggregationDeterminant spreadingB cellsCell responsesActive immune responseMyelin basic proteinLymphoid neogenesisAutoimmune encephalomyelitisMS patientsAggressive diseaseAutoimmune pathologyPatient populationLymphoid organsDisease onsetDisease progressionT cellsImmune responsePathogenic contribution
2010
Focal experimental autoimmune encephalomyelitis in the lewis rat induced by immunization with myelin oligodendrocyte glycoprotein and intraspinal injection of vascular endothelial growth factor
Sasaki M, Lankford KL, Brown RJ, Ruddle NH, Kocsis JD. Focal experimental autoimmune encephalomyelitis in the lewis rat induced by immunization with myelin oligodendrocyte glycoprotein and intraspinal injection of vascular endothelial growth factor. Glia 2010, 58: 1523-1531. PMID: 20645414, DOI: 10.1002/glia.21026.Peer-Reviewed Original ResearchMeSH KeywordsAnalysis of VarianceAnimalsAntibodiesBlood-Brain BarrierCD3 ComplexDisease Models, AnimalEncephalomyelitis, Autoimmune, ExperimentalEnzyme-Linked Immunosorbent AssayFemaleFreund's AdjuvantInjections, SpinalLipidsMicroscopy, Electron, TransmissionMyelin ProteinsMyelin-Associated GlycoproteinMyelin-Oligodendrocyte GlycoproteinRatsRats, Inbred LewSpinal CordTime FactorsVascular Endothelial Growth Factor AConceptsMyelin oligodendrocyte glycoproteinVascular endothelial growth factorExperimental autoimmune encephalomyelitisIncomplete Freund's adjuvantBlood-brain barrierInflammatory demyelinating lesionsLewis ratsEndothelial growth factorDemyelinating lesionsEAE modelAutoimmune encephalomyelitisFreund's adjuvantIntraspinal injectionOligodendrocyte glycoproteinRecombinant rat myelin oligodendrocyte glycoproteinCentral nervous system locationsGrowth factorSensitized T cellsFocal experimental autoimmune encephalomyelitisRat myelin oligodendrocyte glycoproteinSite of injectionMyelin-forming cellsMOG immunizationExtensive demyelinationLymphocyte infiltration
2009
Depletion of CD4+CD25+ T cells exacerbates experimental autoimmune encephalomyelitis induced by mouse, but not rat, antigens
Akirav EM, Bergman CM, Hill M, Ruddle NH. Depletion of CD4+CD25+ T cells exacerbates experimental autoimmune encephalomyelitis induced by mouse, but not rat, antigens. Journal Of Neuroscience Research 2009, 87: 3511-3519. PMID: 19125411, PMCID: PMC4429897, DOI: 10.1002/jnr.21981.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigensAutoantigensAutoimmunityBiomarkersCD4 AntigensCD4-Positive T-LymphocytesCells, CulturedCentral Nervous SystemChemotaxis, LeukocyteDisease Models, AnimalEncephalomyelitis, Autoimmune, ExperimentalFemaleInterferon-gammaInterleukin-10Interleukin-17Interleukin-2 Receptor alpha SubunitLymphocyte ActivationMiceMice, Inbred C57BLMultiple SclerosisMyelin ProteinsMyelin-Associated GlycoproteinMyelin-Oligodendrocyte GlycoproteinRatsT-Lymphocytes, RegulatoryConceptsExperimental autoimmune encephalomyelitisMyelin oligodendrocyte glycoproteinAutoimmune encephalomyelitisT cellsIL-10-producing cellsRegulatory T cellsTissue-restricted antigensCentral nervous systemField of autoimmunityT cell activationTreg depletionEAE severitySelf antigensOligodendrocyte glycoproteinForeign antigensExperimental diseaseNervous systemRelated antigensMiceSelf-antigen specificityAntigenTregsEncephalomyelitisAutoimmunityRats
2007
Regulatory T cells selectively protect against experimental autoimmune encephalomyelitis induced with self but not foreign antigens (B79)
Akirav E, Xu Y, Bergman C, Hill M, Ruddle N. Regulatory T cells selectively protect against experimental autoimmune encephalomyelitis induced with self but not foreign antigens (B79). The Journal Of Immunology 2007, 178: lb16-lb17. DOI: 10.4049/jimmunol.178.supp.b79.Peer-Reviewed Original ResearchMouse myelin oligodendrocyte glycoproteinExperimental autoimmune encephalomyelitisMyelin oligodendrocyte glycoproteinRegulatory T cellsTreg depletionT cellsAutoimmune encephalomyelitisMultiple sclerosisHuman myelin oligodendrocyte glycoproteinRatio of IFNγT cell responsesT cell proliferationCentral nervous systemEAE severityMOG35-55IL17 productionAutoimmune diseasesOligodendrocyte glycoproteinForeign antigensMurine modelNervous systemRelated antigensDisease severityCell responsesMice
2005
Pathogenic myelin oligodendrocyte glycoprotein antibodies recognize glycosylated epitopes and perturb oligodendrocyte physiology
Marta CB, Oliver AR, Sweet RA, Pfeiffer SE, Ruddle NH. Pathogenic myelin oligodendrocyte glycoprotein antibodies recognize glycosylated epitopes and perturb oligodendrocyte physiology. Proceedings Of The National Academy Of Sciences Of The United States Of America 2005, 102: 13992-13997. PMID: 16172404, PMCID: PMC1236555, DOI: 10.1073/pnas.0504979102.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SubstitutionAnimalsAutoantibodiesB-LymphocytesEncephalomyelitis, Autoimmune, ExperimentalGlycosylationHumansImmunizationImmunodominant EpitopesImmunoglobulin GMiceMice, Inbred C57BLMyelin ProteinsMyelin SheathMyelin-Associated GlycoproteinMyelin-Oligodendrocyte GlycoproteinOligodendrogliaProlineRatsSerineConceptsHuman myelin oligodendrocyte glycoproteinMyelin oligodendrocyte glycoproteinExperimental autoimmune encephalomyelitisAnti-MOG antibodiesMultiple sclerosis patientsSclerosis patientsMouse myelin oligodendrocyte glycoproteinB cell-deficient miceMyelin oligodendrocyte glycoprotein antibodyB cell requirementCell-deficient miceAutoimmune encephalomyelitisAntibody pathogenicityPathogenic IgGC57BL/6 miceGlycoprotein antibodiesControl subjectsOligodendrocyte glycoproteinOnly immunizationMOG proteinHigh titersComparable titersMyelin componentsOligodendrocyte physiologyAntigenic determinants
2003
Rat and Human Myelin Oligodendrocyte Glycoproteins Induce Experimental Autoimmune Encephalomyelitis by Different Mechanisms in C57BL/6 Mice
Oliver A, Lyon G, Ruddle N. Rat and Human Myelin Oligodendrocyte Glycoproteins Induce Experimental Autoimmune Encephalomyelitis by Different Mechanisms in C57BL/6 Mice. The Journal Of Immunology 2003, 171: 4934-4934. DOI: 10.4049/jimmunol.171.9.4934.Peer-Reviewed Original ResearchRat and Human Myelin Oligodendrocyte Glycoproteins Induce Experimental Autoimmune Encephalomyelitis by Different Mechanisms in C57BL/6 Mice
Oliver AR, Lyon GM, Ruddle NH. Rat and Human Myelin Oligodendrocyte Glycoproteins Induce Experimental Autoimmune Encephalomyelitis by Different Mechanisms in C57BL/6 Mice. The Journal Of Immunology 2003, 171: 462-468. PMID: 12817031, DOI: 10.4049/jimmunol.171.1.462.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntigen PresentationAutoantibodiesB-LymphocytesCell MovementDose-Response Relationship, ImmunologicEncephalomyelitis, Autoimmune, ExperimentalFemaleGlycoproteinsHumansImmunoglobulin GInjections, IntramuscularInterferon-gammaInterleukin-13MiceMice, Inbred C57BLMice, Mutant StrainsMolecular Sequence DataMyelin-Oligodendrocyte GlycoproteinPeptide FragmentsRatsSpecies SpecificitySpinal CordConceptsExperimental autoimmune encephalomyelitisMyelin oligodendrocyte glycoproteinRat myelin oligodendrocyte glycoproteinHuman myelin oligodendrocyte glycoproteinMOG 35C57BL/6 miceMOG proteinAutoimmune encephalomyelitisOligodendrocyte glycoproteinB cellsCell responsesEncephalitogenic T cell responsesB cell-deficient miceB cell dependenceCell-deficient miceT cell responsesB cell responsesDifferent pathogenic mechanismsCNS infiltratesIL-13T cellsSpleen cellsIFN-gammaIgG subclassesAg presentation
2002
Altered vascular permeability and early onset of experimental autoimmune encephalomyelitis in PECAM-1–deficient mice
Graesser D, Solowiej A, Bruckner M, Osterweil E, Juedes A, Davis S, Ruddle NH, Engelhardt B, Madri JA. Altered vascular permeability and early onset of experimental autoimmune encephalomyelitis in PECAM-1–deficient mice. Journal Of Clinical Investigation 2002, 109: 383-392. PMID: 11827998, PMCID: PMC150854, DOI: 10.1172/jci13595.Peer-Reviewed Original ResearchConceptsExperimental autoimmune encephalomyelitisPECAM-1-deficient miceEndothelial cellsAutoimmune encephalomyelitisVascular permeabilityDevelopment of EAET lymphocyte transendothelial migrationEarly onsetHuman autoimmune disease multiple sclerosisAutoimmune disease multiple sclerosisCell adhesion molecule-1Altered vascular permeabilityCNS vascular permeabilityMononuclear cell extravasationDisease multiple sclerosisPlatelet/endothelial cell adhesion molecule-1Wild-type miceAdhesion molecule-1Endothelial cell adhesion molecule-1Subsets of leukocytesPECAM-1 expressionLymphocyte transendothelial migrationEarly time pointsHistamine challengeMultiple sclerosis
2001
Resident and Infiltrating Central Nervous System APCs Regulate the Emergence and Resolution of Experimental Autoimmune Encephalomyelitis
Juedes A, Ruddle N. Resident and Infiltrating Central Nervous System APCs Regulate the Emergence and Resolution of Experimental Autoimmune Encephalomyelitis. The Journal Of Immunology 2001, 166: 5168-5175. PMID: 11290800, DOI: 10.4049/jimmunol.166.8.5168.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntigen PresentationAntigen-Presenting CellsB7-1 AntigenBrainCell LineCell MovementDown-RegulationEncephalomyelitis, Autoimmune, ExperimentalFemaleGrowth InhibitorsHistocompatibility Antigens Class IHistocompatibility Antigens Class IILymphocyte ActivationMacromolecular SubstancesMacrophagesMiceMice, Inbred C57BLMice, KnockoutMicrogliaMolecular Sequence DataMyelin ProteinsMyelin-Associated GlycoproteinMyelin-Oligodendrocyte GlycoproteinNitric OxideSpinal CordT-LymphocytesConceptsExperimental autoimmune encephalomyelitisT cell proliferationT cellsT cell linesCNS APCCNS APCsAutoimmune encephalomyelitisMHC-IITarget organsInducible NO synthase-deficient miceT cell cytokine productionTh1 T cellsAutoreactive T cellsCell cytokine productionIFN-gamma productionB7-1 expressionSynthase-deficient miceCell proliferationMac-1 cellsCell linesInitiation of diseaseProduction of NOResident microgliaMyelin oligodendrocyteCytokine productionICOS co-stimulatory receptor is essential for T-cell activation and function
Dong C, Juedes A, Temann U, Shresta S, Allison J, Ruddle N, Flavell R. ICOS co-stimulatory receptor is essential for T-cell activation and function. Nature 2001, 409: 97-101. PMID: 11343121, DOI: 10.1038/35051100.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntibody FormationAntigens, CDAntigens, Differentiation, T-LymphocyteCell DifferentiationCells, CulturedEncephalomyelitis, Autoimmune, ExperimentalGene TargetingHemocyaninsInducible T-Cell Co-Stimulator ProteinInterleukin-13Interleukin-4Lymph NodesLymphocyte ActivationMiceMice, KnockoutMolecular Sequence DataMyelin ProteinsMyelin-Associated GlycoproteinMyelin-Oligodendrocyte GlycoproteinT-LymphocytesConceptsInducible co-stimulatory moleculeT cell activationCo-stimulatory moleculesT cellsICOS-/- miceICOS-deficient miceInflammatory autoimmune diseaseExperimental autoimmune encephalomyelitisInjection of lipopolysaccharideCo-stimulatory receptorsHumoral immune responseNon-immune tissuesT lymphocyte activationAutoimmune encephalomyelitisAutoimmune diseasesImmune responseInterleukin-4Immune functionCD28/CTLA4 familyB cellsProtective roleEnhanced susceptibilityActivationReceptorsHigh affinity
2000
Kinetics and Cellular Origin of Cytokines in the Central Nervous System: Insight into Mechanisms of Myelin Oligodendrocyte Glycoprotein-Induced Experimental Autoimmune Encephalomyelitis
Juedes A, Hjelmström P, Bergman C, Neild A, Ruddle N. Kinetics and Cellular Origin of Cytokines in the Central Nervous System: Insight into Mechanisms of Myelin Oligodendrocyte Glycoprotein-Induced Experimental Autoimmune Encephalomyelitis. The Journal Of Immunology 2000, 164: 419-426. PMID: 10605038, DOI: 10.4049/jimmunol.164.1.419.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCentral Nervous SystemChemokinesCytokinesEncephalomyelitis, Autoimmune, ExperimentalFemaleImmunophenotypingInflammation MediatorsInjections, SubcutaneousInterferon-gammaKineticsLymphocyte ActivationMacrophagesMiceMice, Inbred C57BLMicrogliaMolecular Sequence DataMyelin ProteinsMyelin-Associated GlycoproteinMyelin-Oligodendrocyte GlycoproteinSpleenTh1 CellsTh2 CellsTumor Necrosis Factor-alphaConceptsMyelin oligodendrocyte glycoproteinExperimental autoimmune encephalomyelitisAutoimmune encephalomyelitisOligodendrocyte glycoproteinTNF-alphaT cellsDay 7IFN-inducible protein-10TNF-alpha-producing cellsMonocyte chemotactic protein-1MOG35-55 peptideChronic clinical courseAnti-inflammatory cytokinesCD4 T cellsCourse of diseaseChemotactic protein-1Sensitive single-cell assayCellular originTNF-alpha productionRecruitment of macrophagesCentral nervous systemMOG35-55Clinical courseTh1 cytokinesTh2 cytokines