2010
Functionally defective germline variants of sialic acid acetylesterase in autoimmunity
Surolia I, Pirnie SP, Chellappa V, Taylor KN, Cariappa A, Moya J, Liu H, Bell DW, Driscoll DR, Diederichs S, Haider K, Netravali I, Le S, Elia R, Dow E, Lee A, Freudenberg J, De Jager PL, Chretien Y, Varki A, MacDonald ME, Gillis T, Behrens TW, Bloch D, Collier D, Korzenik J, Podolsky DK, Hafler D, Murali M, Sands B, Stone JH, Gregersen PK, Pillai S. Functionally defective germline variants of sialic acid acetylesterase in autoimmunity. Nature 2010, 466: 243-247. PMID: 20555325, PMCID: PMC2900412, DOI: 10.1038/nature09115.Peer-Reviewed Original ResearchMeSH KeywordsAcetylationAcetylesteraseAllelesAnimalsAntibodies, AntinuclearArthritis, RheumatoidAutoimmune DiseasesAutoimmunityBiocatalysisB-LymphocytesCarboxylic Ester HydrolasesCase-Control StudiesCell LineDiabetes Mellitus, Type 1EuropeExonsGenetic Predisposition to DiseaseGerm-Line MutationHumansMiceN-Acetylneuraminic AcidOdds RatioPolymorphism, Single NucleotideSample SizeSequence Analysis, DNA
2009
Engineered Interleukin-2 Antagonists for the Inhibition of Regulatory T Cells
Liu DV, Maier LM, Hafler DA, Wittrup KD. Engineered Interleukin-2 Antagonists for the Inhibition of Regulatory T Cells. Journal Of Immunotherapy 2009, 32: 887-894. PMID: 19816193, PMCID: PMC4078882, DOI: 10.1097/cji.0b013e3181b528da.Peer-Reviewed Original ResearchConceptsIL-2 receptorRegulatory T cellsWild-type IL-2IL-2T cellsIL-2 analogHigh regulatory T cellsIL-2 receptor alphaRegulatory T-cell suppressionInterleukin-2 antagonistsAntitumor immune responseT cell suppressionIL-2 receptor alpha subunitT cell growthT cell linesTreg inhibitionImmunosuppressive effectsCancer patientsSimilar efficacyImmune responseReceptor alpha subunitCell suppressionReceptor alphaAlpha subunitHuman interleukinAntibodies produced by clonally expanded plasma cells in multiple sclerosis cerebrospinal fluid
Owens GP, Bennett JL, Lassmann H, O'Connor KC, Ritchie AM, Shearer A, Lam C, Yu X, Birlea M, DuPree C, Williamson RA, Hafler DA, Burgoon MP, Gilden D. Antibodies produced by clonally expanded plasma cells in multiple sclerosis cerebrospinal fluid. Annals Of Neurology 2009, 65: 639-649. PMID: 19557869, PMCID: PMC2843543, DOI: 10.1002/ana.21641.Peer-Reviewed Original ResearchConceptsMS cerebrospinal fluidMyelin oligodendrocyte glycoproteinMultiple sclerosisCerebrospinal fluidMyelin basic proteinMyelin antigensOligodendrocyte glycoproteinMultiple sclerosis cerebrospinal fluidOligoclonal B cell responseB cell clonal expansionIntrathecal IgG synthesisB cell responsesPlasma cell cloneB lymphocyte clonesHuman brain tissue sectionsTissue sectionsProteolipid proteinIndividual myelin proteinsBasic proteinBrain tissue sectionsIgG synthesisInflammatory cellsHumoral responseControl brainsPlasma cellsAutomated high-dimensional flow cytometric data analysis
Pyne S, Hu X, Wang K, Rossin E, Lin TI, Maier LM, Baecher-Allan C, McLachlan GJ, Tamayo P, Hafler DA, De Jager PL, Mesirov JP. Automated high-dimensional flow cytometric data analysis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 106: 8519-8524. PMID: 19443687, PMCID: PMC2682540, DOI: 10.1073/pnas.0903028106.Peer-Reviewed Original Research
2008
Genetic Analysis of Human Traits In Vitro: Drug Response and Gene Expression in Lymphoblastoid Cell Lines
Choy E, Yelensky R, Bonakdar S, Plenge RM, Saxena R, De Jager PL, Shaw SY, Wolfish CS, Slavik JM, Cotsapas C, Rivas M, Dermitzakis ET, Cahir-McFarland E, Kieff E, Hafler D, Daly MJ, Altshuler D. Genetic Analysis of Human Traits In Vitro: Drug Response and Gene Expression in Lymphoblastoid Cell Lines. PLOS Genetics 2008, 4: e1000287. PMID: 19043577, PMCID: PMC2583954, DOI: 10.1371/journal.pgen.1000287.Peer-Reviewed Original ResearchConceptsLymphoblastoid cell linesBiological noiseGenome-wide significanceInternational HapMap ProjectDrug responseCell linesGenotype-phenotype relationshipsIndividual mRNAsEQTL SNPsGenetic analysisGene expressionHapMap projectHuman cellsHuman traitsNon-genetic factorsQTLMetabolic stateModel systemGenesMRNA levelsBaseline growth ratesSpurious associationsGrowth ratePharmacogenetic experimentsEQTLsIL-21 and TGF-β are required for differentiation of human TH17 cells
Yang L, Anderson DE, Baecher-Allan C, Hastings WD, Bettelli E, Oukka M, Kuchroo VK, Hafler DA. IL-21 and TGF-β are required for differentiation of human TH17 cells. Nature 2008, 454: 350-352. PMID: 18469800, PMCID: PMC2760130, DOI: 10.1038/nature07021.Peer-Reviewed Original ResearchTIM-4 Expressed on APCs Induces T Cell Expansion and Survival
Rodriguez-Manzanet R, Meyers JH, Balasubramanian S, Slavik J, Kassam N, Dardalhon V, Greenfield EA, Anderson AC, Sobel RA, Hafler DA, Strom TB, Kuchroo VK. TIM-4 Expressed on APCs Induces T Cell Expansion and Survival. The Journal Of Immunology 2008, 180: 4706-4713. PMID: 18354194, PMCID: PMC2948965, DOI: 10.4049/jimmunol.180.7.4706.Peer-Reviewed Original Research
2004
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
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
2001
In vitro evidence that immunuaffinity-purified MOG contains immunogenic quantities of contaminating mouse IgG; techniques for producing Ig-free MOG
Ohashi T, Yukitake M, Slavin A, Krieger J, Hafler D. In vitro evidence that immunuaffinity-purified MOG contains immunogenic quantities of contaminating mouse IgG; techniques for producing Ig-free MOG. Journal Of Neuroimmunology 2001, 118: 194-202. PMID: 11498254, DOI: 10.1016/s0165-5728(01)00321-6.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalAntibody SpecificityBlotting, WesternCell LineClone CellsCytokinesElectrophoresis, Polyacrylamide GelEnzyme-Linked Immunosorbent AssayFlow CytometryHumansImmunoglobulin GImmunophenotypingImmunosorbent TechniquesLymphocyte ActivationMiceMultiple SclerosisMyelin ProteinsMyelin SheathMyelin-Associated GlycoproteinMyelin-Oligodendrocyte GlycoproteinSensitivity and SpecificityT-Lymphocytes
1999
T cell Autoreactivity to Proinsulin Epitopes in Diabetic Patients and Healthy Subjects
Semana G, Gausling R, Jackson R, Hafler D. T cell Autoreactivity to Proinsulin Epitopes in Diabetic Patients and Healthy Subjects. Journal Of Autoimmunity 1999, 12: 259-267. PMID: 10330297, DOI: 10.1006/jaut.1999.0282.Peer-Reviewed Original ResearchConceptsProinsulin epitopesImmune responseProliferative responseReactive cellsPeptide-specific T cellsShort-term cell linesSpecific T cell clonesHigher 3H-thymidine incorporationPredominant immune responseT cell autoreactivitySpecific T cellsLow proliferative responseTissue-specific autoantigensT cell clonesCD3-CD28IDDM groupIDDM patientsDiabetic patientsControl subjectsDisease onsetPotential autoantigensStrong TCR signalsC-peptideT cellsHealthy subjectsCross-Reactivity of T-Cell Clones Specific for Altered Peptide Ligands of Myelin Basic Protein
Ausubel L, Bieganowska K, Hafler D. Cross-Reactivity of T-Cell Clones Specific for Altered Peptide Ligands of Myelin Basic Protein. Cellular Immunology 1999, 193: 99-107. PMID: 10202117, DOI: 10.1006/cimm.1998.1447.Peer-Reviewed Original ResearchConceptsT cell clonesT cellsSpecific T cell repertoireAutoreactive T cellsTh1-type cytokinesTh2-type cytokinesMultiple sclerosis patientsT cell repertoireAltered peptide ligandT cell receptor alphaPotential beneficial effectsTCR contact residuesMyelin basic proteinDownregulatory cytokinesSclerosis patientsIL-4IL-5Individual patientsReceptor alphaBeneficial effectsClonal expansionCytokinesPeptide ligandsSubstantial proliferationCross reactivity
1998
Pulse Cyclophosphamide Plus Methylprednisolone Induces Myelin-Antigen-Specific IL-4-Secreting T Cells in Multiple Sclerosis Patients
Takashima H, Smith D, Fukaura H, Khoury S, Hafler D, Weiner H. Pulse Cyclophosphamide Plus Methylprednisolone Induces Myelin-Antigen-Specific IL-4-Secreting T Cells in Multiple Sclerosis Patients. Clinical Immunology 1998, 88: 28-34. PMID: 9683547, DOI: 10.1006/clin.1998.4558.Peer-Reviewed Original ResearchConceptsIL-4-secreting T cellsUntreated MS patientsProgressive MS patientsT cell linesMS patientsIL-4 secretionMyelin basic proteinT cellsMultiple sclerosisMyelin antigensTetanus toxoidTh1-type autoimmune diseaseShort-term T cell linesCell linesPulse cyclophosphamide therapyTh2-type responseIL-4 productionMultiple sclerosis patientsIFN-gamma productionProteolipid proteinImmune deviationPulse cyclophosphamideCyclophosphamide therapySclerosis patientsAutoimmune diseasesIdentification of a T cell subset capable of both IFN-gamma and IL-10 secretion in patients with chronic Borrelia burgdorferi infection.
Pohl-Koppe A, Balashov K, Steere A, Logigian E, Hafler D. Identification of a T cell subset capable of both IFN-gamma and IL-10 secretion in patients with chronic Borrelia burgdorferi infection. The Journal Of Immunology 1998, 160: 1804-10. PMID: 9469440, DOI: 10.4049/jimmunol.160.4.1804.Peer-Reviewed Original ResearchConceptsT cell linesIFN-gamma/ILB. burgdorferi infectionIFN-gammaBurgdorferi infectionT cellsIL-12Lyme patientsCell linesLyme diseaseVigorous humoral immune responseIL-10 secretionExogenous IL-12T cell subsetsT cell populationsHumoral immune responseNovel populationB. burgdorferiBorrelia burgdorferi infectionPrecursor T cellsWhole mononuclear cellsHuman T cellsGroups of subjectsIL-10Cell subsets
1997
Autoantigen recognition by human CD8 T cell clones: enhanced agonist response induced by altered peptide ligands.
Dressel A, Chin JL, Sette A, Gausling R, Höllsberg P, Hafler DA. Autoantigen recognition by human CD8 T cell clones: enhanced agonist response induced by altered peptide ligands. The Journal Of Immunology 1997, 159: 4943-51. PMID: 9366420, DOI: 10.4049/jimmunol.159.10.4943.Peer-Reviewed Original ResearchConceptsT cell clonesCD8 T cell clonesTCR contact residuesHLA-A2Superagonist peptideCell clonesSelf-AgHLA-A2.1 binding motifsHuman autoimmune diseasesAltered peptide ligandMHC class IMyelin peptidesHLA-A2.1Autoimmune diseasesAutoantigen recognitionSecrete cytokinesEffector responsesLow MHCImmune responseAgonist responsesImmunodominant epitopesAgonist peptideAg recognitionContact residuesCytotoxic responseChanges in cytokine secretion induced by altered peptide ligands of myelin basic protein peptide 85-99.
Ausubel LJ, Krieger JI, Hafler DA. Changes in cytokine secretion induced by altered peptide ligands of myelin basic protein peptide 85-99. The Journal Of Immunology 1997, 159: 2502-12. PMID: 9278344, DOI: 10.4049/jimmunol.159.5.2502.Peer-Reviewed Original ResearchAutoimmune DiseasesCell DifferentiationCell LineClone CellsGene Rearrangement, T-LymphocyteHumansImmunodominant EpitopesInterferon-gammaInterleukin-4Interleukin-5Lymphocyte ActivationMultiple SclerosisMyelin Basic ProteinPeptide FragmentsReceptors, Antigen, T-Cell, alpha-betaStructure-Activity RelationshipTh1 CellsTh2 CellsT-Lymphocyte SubsetsOral 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 anergy in CD8 T cells by B cell presentation of antigen.
Höllsberg P, Batra V, Dressel A, Hafler DA. Induction of anergy in CD8 T cells by B cell presentation of antigen. The Journal Of Immunology 1996, 157: 5269-76. PMID: 8955172, DOI: 10.4049/jimmunol.157.12.5269.Peer-Reviewed Original ResearchMeSH KeywordsAntigen-Presenting CellsB7-1 AntigenB-LymphocytesCD40 LigandCD8-Positive T-LymphocytesCell LineClonal AnergyCytotoxicity, ImmunologicGene ExpressionHumansImmunologic MemoryInterleukin-2Lymphocyte ActivationMembrane GlycoproteinsReceptors, Antigen, T-CellSignal TransductionTranscription, GeneticConceptsCD8 T cellsT cell clonesInduction of anergyT cellsB cellsMononuclear cellsB7-1Cell clonesAg stimulationAnergic CD8 T cellsPeptide-pulsed B cellsPeptide-pulsed target cellsCD4 T-cell clonesCD8 T cell clonesSecondary Ag challengeExogenous IL-2B7-2 costimulationB cell presentationT cell anergyIL-2 secretionNormal proliferative responseIL-2 mRNA transcriptionT cell stimulationEarly tyrosine phosphorylationAdequate costimulationAntigen‐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
T cell recognition of immunodominant and cryptic proteolipid protein epitopes in humans.
Markovic-Plese S, Fukaura H, Zhang J, al-Sabbagh A, Southwood S, Sette A, Kuchroo VK, Hafler DA. T cell recognition of immunodominant and cryptic proteolipid protein epitopes in humans. The Journal Of Immunology 1995, 155: 982-92. PMID: 7541828, DOI: 10.4049/jimmunol.155.2.982.Peer-Reviewed Original ResearchConceptsMultiple sclerosisT cellsPLP epitopesMHC class II isotypesPLP-reactive T cellsShort-term T cell linesCryptic epitopesProteolipid proteinT cell responsesT cell recognitionClass II isotypesT cell linesIndividual synthetic peptidesControl subjectsMHC restrictionImmune responseDR2 moleculesProliferative responseImmunodominant epitopesPLP peptidesProtein AgCell responsesCentral nervous system myelin proteinsMyelin proteinsEpitopesIncreased frequency of gamma delta T cells in cerebrospinal fluid and peripheral blood of patients with multiple sclerosis. Reactivity, cytotoxicity, and T cell receptor V gene rearrangements.
Stinissen P, Vandevyver C, Medaer R, Vandegaer L, Nies J, Tuyls L, Hafler DA, Raus J, Zhang J. Increased frequency of gamma delta T cells in cerebrospinal fluid and peripheral blood of patients with multiple sclerosis. Reactivity, cytotoxicity, and T cell receptor V gene rearrangements. The Journal Of Immunology 1995, 154: 4883-94. PMID: 7722338, DOI: 10.4049/jimmunol.154.9.4883.Peer-Reviewed Original ResearchConceptsGamma delta T cell clonesGamma delta T cellsDelta T cellsT cell clonesGamma delta clonesMultiple sclerosisPeripheral bloodT cellsCerebrospinal fluidMS patientsOND patientsCell clonesControl subjectsNormal individualsBacterial superantigen staphylococcal enterotoxin BCentral nervous system demyelinationCSF of patientsSuperantigen staphylococcal enterotoxin BToxic shock syndrome toxin-1Nervous system demyelinationClonal originSecondary inflammatory processesV gene usageSyndrome toxin-1Staphylococcal enterotoxin B