2018
Minimum Information about T Regulatory Cells: A Step toward Reproducibility and Standardization
Fuchs A, Gliwiński M, Grageda N, Spiering R, Abbas AK, Appel S, Bacchetta R, Battaglia M, Berglund D, Blazar B, Bluestone JA, Bornhäuser M, Brinke A, Brusko TM, Cools N, Cuturi MC, Geissler E, Giannoukakis N, Gołab K, Hafler DA, van Ham SM, Hester J, Hippen K, Di Ianni M, Ilic N, Isaacs J, Issa F, Iwaszkiewicz-Grześ D, Jaeckel E, Joosten I, Klatzmann D, Koenen H, van Kooten C, Korsgren O, Kretschmer K, Levings M, Marek-Trzonkowska NM, Martinez-Llordella M, Miljkovic D, Mills KHG, Miranda JP, Piccirillo CA, Putnam AL, Ritter T, Roncarolo MG, Sakaguchi S, Sánchez-Ramón S, Sawitzki B, Sofronic-Milosavljevic L, Sykes M, Tang Q, Vives-Pi M, Waldmann H, Witkowski P, Wood KJ, Gregori S, Hilkens CMU, Lombardi G, Lord P, Martinez-Caceres EM, Trzonkowski P. Minimum Information about T Regulatory Cells: A Step toward Reproducibility and Standardization. Frontiers In Immunology 2018, 8: 1844. PMID: 29379498, PMCID: PMC5775516, DOI: 10.3389/fimmu.2017.01844.Peer-Reviewed Original ResearchAntigen-presenting cellsRegulatory cellsTolerogenic antigen-presenting cellsT regulatory (Treg) cellsClinical applicationPosttransplant complicationsTreg preparationsAllergic diseasesClinical trialsTregsEfficacious treatmentTreg productsCellular therapyStandardized reportingMedicinal productsDifferent preparationsCellsInvestigatorsCD4ComplicationsTherapyDiseaseTrials
2014
Treg Cells Expressing the Coinhibitory Molecule TIGIT Selectively Inhibit Proinflammatory Th1 and Th17 Cell Responses
Joller N, Lozano E, Burkett PR, Patel B, Xiao S, Zhu C, Xia J, Tan TG, Sefik E, Yajnik V, Sharpe AH, Quintana FJ, Mathis D, Benoist C, Hafler DA, Kuchroo VK. Treg Cells Expressing the Coinhibitory Molecule TIGIT Selectively Inhibit Proinflammatory Th1 and Th17 Cell Responses. Immunity 2014, 40: 569-581. PMID: 24745333, PMCID: PMC4070748, DOI: 10.1016/j.immuni.2014.02.012.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell ProliferationCells, CulturedCytokinesEosinophilsFibrinogenForkhead Transcription FactorsGene Expression ProfilingGene Expression RegulationImmunosuppression TherapyLymphocyte ActivationMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicReceptors, ImmunologicRespiratory HypersensitivityTh1-Th2 BalanceT-Lymphocyte SubsetsT-Lymphocytes, RegulatoryConceptsTreg cell subsetsTh2 cell responsesTreg cellsCell subsetsCell responsesProinflammatory T helper 1T effector cell proliferationTreg cell-mediated suppressionFibrinogen-like protein 2Allergic airway inflammationT regulatory (Treg) cellsTh2 cytokine productionSuppression of Th1T helper 1Effector cell proliferationTreg signature genesProinflammatory Th1TIGIT expressionAirway inflammationTh17 cellsRegulatory cellsHelper 1Cytokine productionT cellsImmune response
2011
Identification of T helper type 1–like, Foxp3+ regulatory T cells in human autoimmune disease
Dominguez-Villar M, Baecher-Allan CM, Hafler DA. Identification of T helper type 1–like, Foxp3+ regulatory T cells in human autoimmune disease. Nature Medicine 2011, 17: 673-675. PMID: 21540856, PMCID: PMC3675886, DOI: 10.1038/nm.2389.Peer-Reviewed Original ResearchConceptsTreg cellsT helper type 1Regulatory T cellsT regulatory (Treg) cellsHelper type 1T helper typeHuman autoimmune diseasesHuman Treg cellsRegulatory cellsIL-12Multiple sclerosisAutoimmune diseasesPeripheral bloodHelper typeT cellsSuppressive activityType 1Functional plasticityConsiderable phenotypicCellsSclerosisIFNDiseaseMiceBloodCD2 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
RNA Interference Screen in Primary Human T Cells Reveals FLT3 as a Modulator of IL-10 Levels
Astier AL, Beriou G, Eisenhaure TM, Anderton SM, Hafler DA, Hacohen N. RNA Interference Screen in Primary Human T Cells Reveals FLT3 as a Modulator of IL-10 Levels. The Journal Of Immunology 2009, 184: 685-693. PMID: 20018615, PMCID: PMC3746748, DOI: 10.4049/jimmunol.0902443.Peer-Reviewed Original ResearchConceptsIL-10 levelsRegulatory type 1 (Tr1) cellsIL-10 secretionIL-10 productionT cellsType 1 cellsHuman T cellsIL-10Primary human T cellsPotent anti-inflammatory cytokineHematopoeitic growth factorsAnti-inflammatory cytokinesHuman primary immune cellsT cell functionActivated T cellsAddition of FLPrimary immune cellsT cell activationRegulatory cellsNovel regulatory feedback loopImmune cellsSuppressive activityCell activationFLT3Growth factor
2006
Human regulatory T cells and their role in autoimmune disease
Baecher‐Allan C, Hafler DA. Human regulatory T cells and their role in autoimmune disease. Immunological Reviews 2006, 212: 203-216. PMID: 16903916, DOI: 10.1111/j.0105-2896.2006.00417.x.Peer-Reviewed Original ResearchConceptsRegulatory T cellsAutoimmune diseasesSelf-reactive cellsT cellsHealthy individualsHuman natural regulatory T cellsSelf-reactive T cellsNatural regulatory T cellsHuman regulatory T cellsPathologic T cellsReduced inhibitory functionSpecific autoimmune diseasesT cell populationsMature T cellsT cell maturationNon-responsive stateRegulatory cellsNatural CD4Peripheral circulationImmune systemPatientsDiseaseInhibitory functionNumber of mechanismsCells
2005
Loss of IL-4 Secretion from Human Type 1a Diabetic Pancreatic Draining Lymph Node NKT Cells
Kent SC, Chen Y, Clemmings SM, Viglietta V, Kenyon NS, Ricordi C, Hering B, Hafler DA. Loss of IL-4 Secretion from Human Type 1a Diabetic Pancreatic Draining Lymph Node NKT Cells. The Journal Of Immunology 2005, 175: 4458-4464. PMID: 16177088, DOI: 10.4049/jimmunol.175.7.4458.Peer-Reviewed Original ResearchConceptsT cell clonesINKT cell clonesINKT cellsIL-4Cell clonesNKT cellsLymph nodesCytokine secretionIFN-gammaHuman type 1AType 1AIslet-infiltrating CD4Invariant NKT cellsT cell primingIL-4 secretionRegulation of murineSite of drainageRegulatory cellsDiabetic subjectsCell primingT cellsDiabetic samplesAltered frequencyTCR stimulationSecretionFunctional analysis of highly defined, FACS-isolated populations of human regulatory CD4+CD25+ T cells
Baecher-Allan C, Wolf E, Hafler DA. Functional analysis of highly defined, FACS-isolated populations of human regulatory CD4+CD25+ T cells. Clinical Immunology 2005, 115: 10-18. PMID: 15870015, DOI: 10.1016/j.clim.2005.02.018.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, CDAntigens, Differentiation, B-LymphocyteCD4-Positive T-LymphocytesCD58 AntigensCoculture TechniquesEnzyme-Linked Immunosorbent AssayFlow CytometryHumansImmunoglobulin GImmunophenotypingLeukocyte Common AntigensL-SelectinReceptors, Interleukin-2Receptors, TransferrinT-Lymphocyte SubsetsConceptsCD4 T cellsT cellsTreg cellsRegulatory cellsTotal CD4 T cellsHuman regulatory cellsRegulatory T cellsAutoimmune disease modelsImportance of CD4Regulatory populationImmune homeostasisCD25Suppressive activityCD4Human regulatorySpecific subpopulationsDisease modelsSignificant proportionMiceVivoMurine cellsPotential heterogeneityFuture studiesCellsHuman diseases
2004
Regulatory T cells in type 1 diabetes mellitus
Viglietta V, Baecher-Allan C, Hafler A, Gottlieb P. Regulatory T cells in type 1 diabetes mellitus. Current Opinion In Endocrinology Diabetes And Obesity 2004, 11: 85-90. DOI: 10.1097/01.med.0000129641.34639.2e.Peer-Reviewed Original ResearchRegulatory T cellsType 1 diabetes mellitusType 1 diabetesT cellsDiabetes mellitusT lymphocytesHuman type 1 diabetesΒ-cell antigensNK T cellsTh2-type responseMost healthy subjectsReactive T lymphocytesOnset of diseaseInsulin-producing β-cellsAutoimmune conditionsPeripheral toleranceRegulatory cellsPeripheral deletionSpecific immunizationTh2 cytokinesAutoimmune diseasesHealthy subjectsAntigen reactivityHealthy individualsAnergy induction
2003
CD4+CD25+ Regulatory Cells from Human Peripheral Blood Express Very High Levels of CD25 Ex Vivo
Baecher‐Allan C, Brown JA, Freeman GJ, Hafler DA. CD4+CD25+ Regulatory Cells from Human Peripheral Blood Express Very High Levels of CD25 Ex Vivo. Novartis Foundation Symposia 2003, 252: 67-91. PMID: 14609213, DOI: 10.1002/0470871628.ch6.Peer-Reviewed Original ResearchConceptsT cellsRegulatory cellsPD-1/PD-L1 interactionLigand PD-L1Responder T cellsPD-L1 interactionContact-dependent mannerCo-culture assaysCTLA4 blockadeRegulatory populationPD-1PD-L1HLA-DRMultiple surface antigensCytokine secretionCD45RA expressionSurface antigenEx vivoLevel of expressionModest inductionSuppressive characteristicsFunctional activityHigh levelsCD25CD45ROIsolation and functional characterization of regulatory CD25brightCD4+ T cells from the target organ of patients with rheumatoid arthritis
Cao D, Malmström V, Baecher‐Allan C, Hafler D, Klareskog L, Trollmo C. Isolation and functional characterization of regulatory CD25brightCD4+ T cells from the target organ of patients with rheumatoid arthritis. European Journal Of Immunology 2003, 33: 215-223. PMID: 12594850, DOI: 10.1002/immu.200390024.Peer-Reviewed Original ResearchConceptsT cellsRegulatory cellsRheumatoid arthritisSynovial fluidTarget organsSuch regulatory T cellsFunctional regulatory cellsInflamed knee jointsPathological T cellsActive rheumatoid arthritisAutologous T cellsRegulatory T cellsExperimental animal modelsPeripheral blood originAutoimmune manifestationsRA patientsAutoimmune diseasesPeripheral bloodSame patientAnimal modelsPatientsKnee jointBlood originDiseaseArthritis
2002
Inhibition of Human CD4+CD25+high Regulatory T Cell Function
Baecher-Allan C, Viglietta V, Hafler DA. Inhibition of Human CD4+CD25+high Regulatory T Cell Function. The Journal Of Immunology 2002, 169: 6210-6217. PMID: 12444126, DOI: 10.4049/jimmunol.169.11.6210.Peer-Reviewed Original ResearchMeSH KeywordsAntigensCD4-Positive T-LymphocytesCoculture TechniquesCytokinesGlucocorticoid-Induced TNFR-Related ProteinHumansImmune ToleranceInterleukin-10Lymphocyte ActivationModels, ImmunologicalReceptors, Interleukin-2Receptors, Nerve Growth FactorReceptors, Tumor Necrosis FactorSignal TransductionT-Lymphocyte SubsetsTransforming Growth Factor betaConceptsAutoreactive T cellsT cellsRegulatory cellsRegulatory T cell functionInflammatory immune responseT cell functionStrength of stimulationPathologic responseInhibition of humanMicrobial AgsResponder cellsImmune responseEffector functionsTCR stimuliTime pointsCell functionTCR signalsPotent regulatorDifferential activationExtent of suppressionStimulationActivationCellsSuppressionStimuli
2001
CD4+CD25high Regulatory Cells in Human Peripheral Blood
Baecher-Allan C, Brown J, Freeman G, Hafler D. CD4+CD25high Regulatory Cells in Human Peripheral Blood. The Journal Of Immunology 2001, 167: 1245-1253. PMID: 11466340, DOI: 10.4049/jimmunol.167.3.1245.Peer-Reviewed Original ResearchMeSH KeywordsAbataceptAntigens, CDAntigens, DifferentiationB7-1 AntigenB7-H1 AntigenBlood ProteinsCD4 AntigensCD4-Positive T-LymphocytesCells, CulturedCoculture TechniquesCTLA-4 AntigenHLA-DR AntigensHumansImmunoconjugatesImmunosuppressive AgentsInterleukin-2KineticsLeukocyte Common AntigensLymphocyte ActivationLymphocyte CountMembrane GlycoproteinsPeptidesReceptors, Antigen, T-CellReceptors, Interleukin-2RNA, MessengerSignal TransductionT-Lymphocyte SubsetsConceptsRegulatory T cellsRegulatory cellsT cellsPD-1/PD-L1Regulatory CD4 T cellsAnti-CD3 stimulusCD4 T cellsHuman autoimmune disordersMultiorgan autoimmune diseasePeripheral lymphoid tissuesRegulatory cell functionIL-2 receptorPD-L1 receptorCirculation of humansHuman peripheral bloodContact-dependent mannerNeonatal day 3B7 pathwayPD-L1Regulatory populationAutoimmune disordersAutoimmune diseasesPeripheral bloodResponder cellsIL-2
1994
Oral 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