2011
CD2 Costimulation Reveals Defective Activity by Human CD4+CD25hi Regulatory Cells in Patients with Multiple Sclerosis
Baecher-Allan CM, Costantino CM, Cvetanovich GL, Ashley CW, Beriou G, Dominguez-Villar M, Hafler DA. CD2 Costimulation Reveals Defective Activity by Human CD4+CD25hi Regulatory Cells in Patients with Multiple Sclerosis. The Journal Of Immunology 2011, 186: 3317-3326. PMID: 21300823, PMCID: PMC4467560, DOI: 10.4049/jimmunol.1002502.Peer-Reviewed Original ResearchMeSH KeywordsAdultCD2 AntigensCD4 AntigensCell DifferentiationCells, CulturedCoculture TechniquesFetal BloodForkhead Transcription FactorsHumansInfant, NewbornInterleukin-2 Receptor alpha SubunitInterleukin-7 Receptor alpha SubunitLymphocyte ActivationMiddle AgedMultiple SclerosisSignal TransductionT-Lymphocyte SubsetsT-Lymphocytes, RegulatoryYoung AdultConceptsMultiple sclerosisIL-17Suppressive capacityDR cellsRegulatory T cell populationEffector T cellsExpression of CD127T cell populationsMechanism of actionTreg populationRegulatory cellsIL-10Effector cellsHLA-DREffector subsetsHuman TregsCD2 costimulationMemory TregsT cellsTregsAdult bloodLow expressionSclerosisPatientsCD127
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 ResearchMeSH KeywordsCell LineCells, CulturedHumansInterleukin-2Interleukin-2 Receptor alpha SubunitJanus KinasesMutant ProteinsPhosphorylationProtein EngineeringSignal TransductionSTAT5 Transcription FactorT-Lymphocytes, RegulatoryConceptsIL-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 interleukinSoluble IL-2RA Levels in Multiple Sclerosis Subjects and the Effect of Soluble IL-2RA on Immune Responses
Maier LM, Anderson DE, Severson CA, Baecher-Allan C, Healy B, Liu DV, Wittrup KD, De Jager PL, Hafler DA. Soluble IL-2RA Levels in Multiple Sclerosis Subjects and the Effect of Soluble IL-2RA on Immune Responses. The Journal Of Immunology 2009, 182: 1541-1547. PMID: 19155502, PMCID: PMC3992946, DOI: 10.4049/jimmunol.182.3.1541.Peer-Reviewed Original ResearchConceptsMultiple sclerosisIL-2 receptorMS subjectsHealthy controlsOrgan-specific autoimmune disordersChronic systemic inflammationType 1 diabetesT cell proliferationMultiple sclerosis subjectsStrong genetic factorIL-2 signalingSIL-2RaSystemic inflammationAutoimmune disordersImmunological perturbationsAutoimmune diseasesIL-2RAControl subjectsMS casesSerum concentrationsDisease onsetSpecific allelic variantsImmune responseAggressive formDisease riskIL2RA Genetic Heterogeneity in Multiple Sclerosis and Type 1 Diabetes Susceptibility and Soluble Interleukin-2 Receptor Production
Maier LM, Lowe CE, Cooper J, Downes K, Anderson DE, Severson C, Clark PM, Healy B, Walker N, Aubin C, Oksenberg JR, Hauser SL, Compston A, Sawcer S, , De Jager PL, Wicker LS, Todd JA, Hafler DA. IL2RA Genetic Heterogeneity in Multiple Sclerosis and Type 1 Diabetes Susceptibility and Soluble Interleukin-2 Receptor Production. PLOS Genetics 2009, 5: e1000322. PMID: 19119414, PMCID: PMC2602853, DOI: 10.1371/journal.pgen.1000322.Peer-Reviewed Original ResearchMeSH KeywordsAdultAllelesCase-Control StudiesDiabetes Mellitus, Type 1Disease SusceptibilityGenetic HeterogeneityGenetic Predisposition to DiseaseGenotypeHumansInterleukin-2 Receptor alpha SubunitMultiple SclerosisSolubilityConceptsMultiple sclerosisT1D subjectsSoluble interleukin-2 receptor productionSoluble interleukin-2 receptorOrgan-specific autoimmune disordersHealthy control subjectsInterleukin-2 receptorType 1 diabetesHuman leukocyte antigen (HLA) complexMS risk genesAutoimmune disordersControl subjectsAutoimmunity riskHealthy controlsIL2RA regionType 1Autoimmune lociRisk allelesReceptor productionCandidate gene association studiesAntigen complexGene association studiesAssociation studiesT1D.Sclerosis
2007
Risk Alleles for Multiple Sclerosis Identified by a Genomewide Study
Hafler D, Compston A, Sawcer S, Lander E, Daly M, De Jager P, de Bakker P, Gabriel S, Mirel D, Ivinson A, Pericak-Vance M, Gregory S, Rioux J, McCauley J, Haines J, Barcellos L, Cree B, Oksenberg J, Hauser S. Risk Alleles for Multiple Sclerosis Identified by a Genomewide Study. New England Journal Of Medicine 2007, 357: 851-862. PMID: 17660530, DOI: 10.1056/nejmoa073493.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAllelesFemaleGenetic Predisposition to DiseaseGenome, HumanHLA-DR alpha-ChainsHLA-DR AntigensHumansInterleukin-2 Receptor alpha SubunitInterleukin-7 Receptor alpha SubunitLinkage DisequilibriumMaleMiddle AgedMultiple SclerosisMutationOligonucleotide Array Sequence AnalysisPolymorphism, Single NucleotideRisk FactorsConceptsMultiple sclerosisReceptor alpha geneSingle nucleotide polymorphismsControl subjectsCase subjectsInterleukin-7 receptor alpha geneHeritable risk factorsAlpha geneRisk factorsFamily triosSclerosisRisk allelesHLA lociHLA-DRA locusTransmission disequilibrium testStringent P valueP-valueEffect sizeSignificant heritable componentInterleukin-2 receptor alpha geneNonsynonymous single nucleotide polymorphismsGenomewide association studiesMultiple single nucleotide polymorphismsSubjectsAssociation
2006
The Purification and Functional Analysis of Human CD4+CD25high Regulatory T Cells
Baecher-Allan C, Hafler DA. The Purification and Functional Analysis of Human CD4+CD25high Regulatory T Cells. Current Protocols In Immunology 2006, 72: 7.4b.1-7.4b.12. PMID: 18432975, DOI: 10.1002/0471142735.im0704bs72.Peer-Reviewed Original ResearchMeSH KeywordsFlow CytometryHumansImmunomagnetic SeparationInterleukin-2 Receptor alpha SubunitT-Lymphocytes, RegulatoryConceptsRegulatory T cellsCD4 T cellsT cellsHuman regulatory T cellsHuman CD4 T cellsLevels of CD25Suppressive featuresCD25Coculture assaysVitro proliferationHigh expressionVivo developmentEndogenous expressionSuch cellsCellsSmall percentageMouse cellsHigh levelsAutoimmunityHumansExpressionMiceBlood