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 toleranceTreatment of Uveitis by Oral Administration of Retinal Antigens: Results of a Phase I/II Randomized Masked Trial
Nussenblatt R, Gery I, Weiner H, Ferris F, Shiloach J, Remaley N, Perry C, Caspi R, Hafler D, Foster C, Whitcup S. Treatment of Uveitis by Oral Administration of Retinal Antigens: Results of a Phase I/II Randomized Masked Trial. American Journal Of Ophthalmology 1997, 123: 583-592. PMID: 9152063, DOI: 10.1016/s0002-9394(14)71070-0.Peer-Reviewed Original ResearchConceptsPhase I/IISoluble retinal antigenTreatment of uveitisRetinal antigensRetinal S-antigenS-antigenStudy endpointImmunosuppressive therapyOral administrationPhase I/II studyMasked trialOcular inflammatory attacksStandard immunosuppressive therapySystemic immunosuppressive therapyPrimary study endpointSecondary study endpointsMain study endpointImmunosuppressive medicationsII studyInflammatory attacksOcular inflammationCytotoxic medicationsImmunosuppressive agentsEndogenous uveitisTreatment groupsOral Administration of Myelin Induces Antigen‐specific TGF‐β1‐secreting T Cells in Multiple Sclerosis Patientsa
KENT S, FUKAURA H, PIETRUSEWICZ M, KHOURY S, WEINER H, HAFLER D. Oral Administration of Myelin Induces Antigen‐specific TGF‐β1‐secreting T Cells in Multiple Sclerosis Patientsa. Annals Of The New York Academy Of Sciences 1997, 815: 412-422. PMID: 9186687, DOI: 10.1111/j.1749-6632.1997.tb52092.x.Peer-Reviewed Original Research
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 clonesPilot Study of Oral Tolerance to Keyhole Limpet Hemocyanin in Humans.
MATSUI M, HAFLER D, WEINER H. Pilot Study of Oral Tolerance to Keyhole Limpet Hemocyanin in Humans. Annals Of The New York Academy Of Sciences 1996, 778: 398-404. PMID: 8611003, DOI: 10.1111/j.1749-6632.1996.tb21156.x.Peer-Reviewed Original ResearchThree‐year Open Protocol Continuation Study of Oral Tolerization with Myelin Antigens in Multiple Sclerosis and Design of a Phase III Pivotal Trial
HOHOL M, KHOURY S, COOK S, ORAV E, HAFLER D, WEINER H. Three‐year Open Protocol Continuation Study of Oral Tolerization with Myelin Antigens in Multiple Sclerosis and Design of a Phase III Pivotal Trial. Annals Of The New York Academy Of Sciences 1996, 778: 243-250. PMID: 8610977, DOI: 10.1111/j.1749-6632.1996.tb21132.x.Peer-Reviewed Original ResearchAntigen‐specific TGF‐β1 Secretion with Bovine Myelin Oral Tolerization in Multiple Sclerosis
FUKAURA H, KENT S, PIETRUSEWICZ M, KHOURY S, WEINER H, HAFLER D. Antigen‐specific TGF‐β1 Secretion with Bovine Myelin Oral Tolerization in Multiple Sclerosis. Annals Of The New York Academy Of Sciences 1996, 778: 251-257. PMID: 8610978, DOI: 10.1111/j.1749-6632.1996.tb21133.x.Peer-Reviewed Original ResearchConceptsRelapsing-remitting MS patientsHuman autoimmune diseasesOral tolerizationMultiple sclerosisAutoimmune diseasesT cell linesMS patientsCytokine secretionT cellsAutoreactive T-cell populationsAutoreactive T cellsT cell populationsT-cell fractionCNS white matterFed patientsIL-4Inflammatory responseΒ1 secretionIFN-gammaTolerizationWhite matterPatientsSclerosisBovine myelinSecretion
1995
Antigen specific therapies for the treatment of autoimmune diseases.
Hafler DA, Weiner HL. Antigen specific therapies for the treatment of autoimmune diseases. 1995, 47: 59-77. PMID: 7785504, DOI: 10.1007/978-3-0348-7343-7_5.Peer-Reviewed Original Research
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 modelsOral 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
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 groupPatientsBiological activity of recombinant human myelin basic protein
Oettinger H, Al-Sabbagh A, Jingwu Z, LaSalle J, Weiner H, Hafler D. Biological activity of recombinant human myelin basic protein. Journal Of Neuroimmunology 1993, 44: 157-162. PMID: 7685037, DOI: 10.1016/0165-5728(93)90037-y.Peer-Reviewed Original ResearchConceptsRecombinant human myelin basic proteinRecombinant protein bindsRecombinant MBPInducible expression vectorBasic proteinMyelin basic proteinRecombinant protein preparationsProtein bindsHuman myelin basic proteinRecombinant proteinsExpression vectorEscherichia coliProtein preparationsProteinNative MBPE. coliCation exchange chromatographySDS-PAGEBiological reagentsSimilar affinityHuman MBPColiBiological activitySimilar conformationsCell clones
1991
Antigen‐Driven Peripheral Immune Tolerance
WEINER H, ZHANG Z, KHOURY S, MILLER A, AL‐SABBAGH A, BROD S, LIDER O, HIGGINS P, SOBEL R, NUSSENBLATT R, HAFLER D. Antigen‐Driven Peripheral Immune Tolerance. Annals Of The New York Academy Of Sciences 1991, 636: 227-232. PMID: 1793212, DOI: 10.1111/j.1749-6632.1991.tb33454.x.Peer-Reviewed Original ResearchSuppression 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
1987
Secondary immune amplification following live poliovirus immunization in humans
Hafler D, Fox D, Benjamin D, Blue M, Weiner H. Secondary immune amplification following live poliovirus immunization in humans. Clinical Immunology 1987, 44: 321-328. PMID: 3040309, DOI: 10.1016/0090-1229(87)90076-6.Peer-Reviewed Original ResearchConceptsAutologous mixed lymphocyte responseRecall antigensAnamnestic responseImmune amplificationImmune responseHuman T cell responsesT cell proliferative responsesLive virus infectionT cell responsesMixed lymphocyte responseSecondary immune responsePoliovirus immunizationLymphocyte responsesVirus infectionProliferative responsePoliovirus infectionAntigenPotential mechanismsAmplification pathwayConsistent changesImmunizationInfectionPoliovirusSubjectsResponse