2008
CTLA4Ig treatment in patients with multiple sclerosis
Viglietta V, Bourcier K, Buckle GJ, Healy B, Weiner HL, Hafler DA, Egorova S, Guttmann CR, Rusche JR, Khoury SJ. CTLA4Ig treatment in patients with multiple sclerosis. Neurology 2008, 71: 917-924. PMID: 18794494, DOI: 10.1212/01.wnl.0000325915.00112.61.Peer-Reviewed Original ResearchConceptsMultiple sclerosisCostimulatory pathwayPhase 1 dose-escalation studyT cell-mediated autoimmune diseaseCell-mediated autoimmune diseaseRelapsing-remitting multiple sclerosisT-cell costimulatory pathwaysCostimulatory molecule interactionsMonths of infusionDose-escalation studyInterferon-gamma productionT cell activationOriginal therapeutic approachAdverse eventsImmunologic assessmentImmunologic effectsCTLA4Ig treatmentChronic inflammationAutoimmune diseasesInflammatory processT cellsImmune responseTherapeutic approachesCTLA4IgExtension study
2006
Innate Immunity in Multiple Sclerosis: Myeloid Dendritic Cells in Secondary Progressive Multiple Sclerosis Are Activated and Drive a Proinflammatory Immune Response
Karni A, Abraham M, Monsonego A, Cai G, Freeman GJ, Hafler D, Khoury SJ, Weiner HL. Innate Immunity in Multiple Sclerosis: Myeloid Dendritic Cells in Secondary Progressive Multiple Sclerosis Are Activated and Drive a Proinflammatory Immune Response. The Journal Of Immunology 2006, 177: 4196-4202. PMID: 16951385, DOI: 10.4049/jimmunol.177.6.4196.Peer-Reviewed Original ResearchConceptsMyeloid dendritic cellsDendritic cellsMultiple sclerosisInnate immune systemRR-MSImmune responseImmune systemT cell-mediated autoimmune diseaseSecondary progressive multiple sclerosisCell-mediated autoimmune diseaseStages of MSIncreased percentageProgressive phaseNeuronal degenerative changesSecondary progressive phaseSP-MS patientsProgressive multiple sclerosisProinflammatory immune responsePrimary immune responseNaive T cellsImmunologic basisTh1 responseClinical patternMS patientsPD-L1
2004
An Autoimmune Disease-Associated CTLA-4 Splice Variant Lacking the B7 Binding Domain Signals Negatively in T Cells
Vijayakrishnan L, Slavik JM, Illés Z, Greenwald RJ, Rainbow D, Greve B, Peterson LB, Hafler DA, Freeman GJ, Sharpe AH, Wicker LS, Kuchroo VK. An Autoimmune Disease-Associated CTLA-4 Splice Variant Lacking the B7 Binding Domain Signals Negatively in T Cells. Immunity 2004, 20: 563-575. PMID: 15142525, DOI: 10.1016/s1074-7613(04)00110-4.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntigens, CDAntigens, DifferentiationAutoimmune DiseasesB7-1 AntigenBlotting, WesternCloning, MolecularCTLA-4 AntigenFemaleFlow CytometryHumansMembrane ProteinsMiceMice, Inbred NODMolecular Sequence DataReceptors, Antigen, T-CellReverse Transcriptase Polymerase Chain ReactionRNA, MessengerSignal TransductionT-LymphocytesConceptsCytotoxic T-lymphocyte-associated antigen 4T cell responsesT cellsNOD miceAutoimmune diseasesT cell-mediated autoimmune diseaseT-lymphocyte-associated antigen 4Cell responsesCell-mediated autoimmune diseaseSusceptible NOD miceRegulatory T cellsNOD congenic miceCTLA-4 locusAntigen-4B7-1B7-2Primary T cellsCongenic miceSplice variantsMiceNegative signalingMYPPPY motifDiseaseType IGenetic linkage
1997
Oral Administration of Myelin Induces Antigen‐specific TGF‐β1 Secreting T Cells in Patients with Multiple Sclerosisa
HAFLER D, KENT S, PIETRUSEWICZ M, KHOURY S, WEINER H, FUKAURA H. Oral Administration of Myelin Induces Antigen‐specific TGF‐β1 Secreting T Cells in Patients with Multiple Sclerosisa. Annals Of The New York Academy Of Sciences 1997, 835: 120-131. PMID: 9616767, DOI: 10.1111/j.1749-6632.1997.tb48623.x.Peer-Reviewed Original ResearchConceptsMultiple sclerosisT cellsAutoimmune diseasesOral administrationT cell linesNon-treated MS patientsPLP-reactive T cellsTh1-type autoimmune diseaseShort-term T cell linesCell-mediated autoimmune diseaseOriginal T cell cloneSystemic immune toleranceExperimental autoimmune diseasesNon-treated patientsRegulatory T cellsRelapsing-remitting patientsIFN-gamma secretionT cell clonesCell linesMultiple sclerosisAOral tolerizationOral toleranceMS patientsAutoimmune cascadeImmune toleranceImmune deviation following pulse cyclophosphamide/methylprednisolone treatment of multiple sclerosis: Increased interleukin‐4 production and associated eosinophilia
Smith D, Balashov K, Hafler D, Khoury S, Weiner H. Immune deviation following pulse cyclophosphamide/methylprednisolone treatment of multiple sclerosis: Increased interleukin‐4 production and associated eosinophilia. Annals Of Neurology 1997, 42: 313-318. PMID: 9307252, DOI: 10.1002/ana.410420307.Peer-Reviewed Original ResearchConceptsMonthly intravenous methylprednisolonePulse cyclophosphamide therapyMultiple sclerosisImmune deviationIL-4Cyclophosphamide therapyIFN-beta1bMS patientsHealthy controlsTh1-type cell-mediated autoimmune diseaseCell-mediated autoimmune diseaseMethotrexate-treated patientsT-cell interferonUntreated MS patientsUntreated multiple sclerosisPeripheral blood eosinophiliaProgressive MS patientsTh2-type responseCyclophosphamide-treated patientsIL-10 productionInterleukin-4 productionMinimal IL-4Intravenous cyclophosphamideIntravenous methylprednisoloneBlood eosinophiliaIncreased interleukin 12 production in progressive multiple sclerosis: Induction by activated CD4+ T cells via CD40 ligand
Balashov K, Smith D, Khoury S, Hafler D, Weiner H. Increased interleukin 12 production in progressive multiple sclerosis: Induction by activated CD4+ T cells via CD40 ligand. Proceedings Of The National Academy Of Sciences Of The United States Of America 1997, 94: 599-603. PMID: 9012830, PMCID: PMC19559, DOI: 10.1073/pnas.94.2.599.Peer-Reviewed Original ResearchConceptsIL-12 secretionIFN-gamma secretionMS patientsMultiple sclerosisT cellsIL-12Anti-CD40 ligand antibodyTh1-type immune activationCell-mediated autoimmune diseaseProgressive MS patientsProgressive multiple sclerosisIFN-gamma administrationRelapsing-remitting patientsExacerbation of diseaseInterleukin-12 productionChronic inflammatory diseaseCD40 ligand expressionCentral nervous systemActivated T cellsImmune interventionImmune activationAutoimmune diseasesInterleukin-12Inflammatory diseasesCD40 ligand
1996
Induction of circulating myelin basic protein and proteolipid protein-specific transforming growth factor-beta1-secreting Th3 T cells by oral administration of myelin in multiple sclerosis patients.
Fukaura H, Kent SC, Pietrusewicz MJ, Khoury SJ, Weiner HL, Hafler DA. Induction of circulating myelin basic protein and proteolipid protein-specific transforming growth factor-beta1-secreting Th3 T cells by oral administration of myelin in multiple sclerosis patients. Journal Of Clinical Investigation 1996, 98: 70-77. PMID: 8690806, PMCID: PMC507402, DOI: 10.1172/jci118779.Peer-Reviewed Original ResearchConceptsMyelin basic proteinT cellsOral administrationAutoimmune diseasesTetanus toxoidT cell linesMS patientsMultiple sclerosisProteolipid proteinFrequency of MBPNon-treated MS patientsPLP-reactive T cellsTh1-type autoimmune diseaseShort-term T cell linesCell-mediated autoimmune diseaseRelapsing-remitting MS patientsOriginal T cell cloneSpecific IFN-gammaSystemic immune toleranceExperimental autoimmune diseasesRegulatory T cellsReactive T cellsIFN-gamma secretionMultiple sclerosis patientsT cell clones
1995
Expression of costimulatory molecules B7-1 (CD80), B7-2 (CD86), and interleukin 12 cytokine in multiple sclerosis lesions.
Windhagen A, Newcombe J, Dangond F, Strand C, Woodroofe MN, Cuzner ML, Hafler DA. Expression of costimulatory molecules B7-1 (CD80), B7-2 (CD86), and interleukin 12 cytokine in multiple sclerosis lesions. Journal Of Experimental Medicine 1995, 182: 1985-1996. PMID: 7500044, PMCID: PMC2192240, DOI: 10.1084/jem.182.6.1985.Peer-Reviewed Original ResearchConceptsAutoreactive T cellsMultiple sclerosisT cellsB7-1Autoimmune diseasesCostimulatory moleculesMS plaquesB7-2T cell-mediated autoimmune diseaseInitiation of MSMyelin-autoreactive T cellsCell-mediated autoimmune diseaseSelf-reactive T cellsCostimulatory molecules B7-1Acute MS plaquesAutoimmune animal modelsInterleukin-12 cytokinesPutative autoimmune diseaseSemiquantitative reverse transcriptase-polymerase chain reactionReverse transcriptase-polymerase chain reactionExpression of cytokinesTranscriptase-polymerase chain reactionT cell activationMultiple sclerosis lesionsInflammatory cuffsTherapy for Multiple Sclerosis
Weiner H, Hohol M, Khoury S, Dawson D, Hafler D. Therapy for Multiple Sclerosis. Neurologic Clinics 1995, 13: 173-196. PMID: 7739502, DOI: 10.1016/s0733-8619(18)30066-5.Peer-Reviewed Original ResearchConceptsMultiple sclerosisCell-mediated autoimmune diseaseAccumulation of disabilityMultiple sclerosis patientsSymptomatic therapySclerosis patientsAutoimmune responseCentral nervous system myelinAutoimmune diseasesNonspecific modulationImmune systemSclerosisSystem myelinTherapyImmunotherapyPatientsDiseaseMyelin
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 models
1993
Effects of Oral Administration of Type II Collagen on Rheumatoid Arthritis
Trentham D, Dynesius-Trentham R, Orav E, Combitchi D, Lorenzo C, Sewell K, Hafler D, Weiner H. Effects of Oral Administration of Type II Collagen on Rheumatoid Arthritis. Science 1993, 261: 1727-1730. PMID: 8378772, DOI: 10.1126/science.8378772.Peer-Reviewed Original ResearchConceptsRheumatoid arthritisType II collagenT cell-mediated autoimmune diseaseCell-mediated autoimmune diseaseChicken type II collagenII collagenActive rheumatoid arthritisDouble-blind trialOral tolerizationTender jointsTolerization approachComplete remissionSwollen jointsClinical efficacySynovial diseaseAutoimmune diseasesPotential autoantigensOral administrationT cellsArthritisSide effectsAnimal modelsDiseaseCollagen groupPatients