2018
Activated β-catenin in Foxp3+ regulatory T cells links inflammatory environments to autoimmunity
Sumida T, Lincoln MR, Ukeje CM, Rodriguez DM, Akazawa H, Noda T, Naito AT, Komuro I, Dominguez-Villar M, Hafler DA. Activated β-catenin in Foxp3+ regulatory T cells links inflammatory environments to autoimmunity. Nature Immunology 2018, 19: 1391-1402. PMID: 30374130, PMCID: PMC6240373, DOI: 10.1038/s41590-018-0236-6.Peer-Reviewed Original ResearchConceptsProstaglandin E receptor 2Regulatory T cellsTreg cellsT cellsAnti-inflammatory cytokine productionIL-10 productionPeripheral immune toleranceIL-10 expressionΒ-cateninE receptor 2Treg subpopulationsTreg phenotypeIL-10Cytokines IFNImmune toleranceTreg signatureCytokine signatureMultiple sclerosisAutoimmune diseasesCytokine productionInflammatory environmentLethal autoimmunityReceptor 2Activated β-cateninIFN
2015
Functional inflammatory profiles distinguish myelin-reactive T cells from patients with multiple sclerosis
Cao Y, Goods BA, Raddassi K, Nepom GT, Kwok WW, Love JC, Hafler DA. Functional inflammatory profiles distinguish myelin-reactive T cells from patients with multiple sclerosis. Science Translational Medicine 2015, 7: 287ra74. PMID: 25972006, PMCID: PMC4497538, DOI: 10.1126/scitranslmed.aaa8038.Peer-Reviewed Original ResearchConceptsMyelin-reactive T cellsMultiple sclerosisT cellsHealthy controlsT cell librariesT helper cell 17Antigen-specific T cellsGene signatureMore IL-10More proinflammatory cytokinesAutoreactive T cellsIL-10 productionHuman autoimmune diseasesGranulocyte-macrophage colony-stimulating factorProduction of interferonColony-stimulating factorMyelin antigensTh17 cellsIL-10Inflammatory profileInterleukin-17Proinflammatory cytokinesAutoimmune diseasesDisease progressionHealthy subjects
2014
TLR‐mediated STAT3 and ERK activation controls IL‐10 secretion by human B cells
Liu B, Cao Y, Huizinga TW, Hafler DA, Toes RE. TLR‐mediated STAT3 and ERK activation controls IL‐10 secretion by human B cells. European Journal Of Immunology 2014, 44: 2121-2129. PMID: 24737107, DOI: 10.1002/eji.201344341.Peer-Reviewed Original ResearchConceptsIL-10 productionIL-10-producing B cellsB cellsHuman B cellsIL-10IL-10 secretionPotent immunoregulatory cytokineType I IFNERK activationType I IFN familyInhibition of STAT3TLR-MyD88Activation of STAT3Immunoregulatory cytokinesTLR signalingPotent productionMouse modelI IFNCD40 ligationAntibody productionTLRSTAT3 pathwayIFNIFN familyPotential target
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
2010
IL-12 induces human CD4+CD45RA-CD25hiCD127low/neg regulatory T cells to secrete IFNγ and IL-10 and acquire a non-regulatory effector phenotype (138.9)
Dominguez-Villar M, Hafler D, Baecher-Allan C. IL-12 induces human CD4+CD45RA-CD25hiCD127low/neg regulatory T cells to secrete IFNγ and IL-10 and acquire a non-regulatory effector phenotype (138.9). The Journal Of Immunology 2010, 184: 138.9-138.9. DOI: 10.4049/jimmunol.184.supp.138.9.Peer-Reviewed Original ResearchRegulatory T cellsT cellsEffector phenotypeTreg functionIL-10Immune responseHuman Treg functionCD4 T cellsT cell responsesIL-12 familyIL-12 inducesTreg suppressionPeripheral toleranceCytokine milieuT-betIFN-gammaTregsImmune systemCell responsesCytokinesRecent evidencePivotal roleCellsPhenotypeDistinct effectsMonocytes from Patients with Type 1 Diabetes Have Increased Gene Expression of Pro-inflammatory Cytokines or IL-10
Bradshaw E, Elyaman W, Raddassi K, Mousissian N, Greer A, Orban T, Gottlieb P, Kent S, Hafler D. Monocytes from Patients with Type 1 Diabetes Have Increased Gene Expression of Pro-inflammatory Cytokines or IL-10. Clinical Immunology 2010, 135: s19. DOI: 10.1016/j.clim.2010.03.061.Peer-Reviewed Original ResearchIL-12 Induces Human CD4+CD45RA-CD25hiCD127low/neg Regulatory T Cells to Secrete IFNγ and IL-10 and Acquire a Non-regulatory Effector Phenotype
Dominguez-Villar M, Hafler D, Baecher-Allan C. IL-12 Induces Human CD4+CD45RA-CD25hiCD127low/neg Regulatory T Cells to Secrete IFNγ and IL-10 and Acquire a Non-regulatory Effector Phenotype. Clinical Immunology 2010, 135: s132-s133. DOI: 10.1016/j.clim.2010.03.400.Peer-Reviewed Original Research
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 factorTIM‐3 is expressed on activated human CD4+ T cells and regulates Th1 and Th17 cytokines
Hastings WD, Anderson DE, Kassam N, Koguchi K, Greenfield EA, Kent SC, Zheng XX, Strom TB, Hafler DA, Kuchroo VK. TIM‐3 is expressed on activated human CD4+ T cells and regulates Th1 and Th17 cytokines. European Journal Of Immunology 2009, 39: 2492-2501. PMID: 19676072, PMCID: PMC2759376, DOI: 10.1002/eji.200939274.Peer-Reviewed Original Research
2006
Alterations in CD46-mediated Tr1 regulatory T cells in patients with multiple sclerosis
Astier AL, Meiffren G, Freeman S, Hafler DA. Alterations in CD46-mediated Tr1 regulatory T cells in patients with multiple sclerosis. Journal Of Clinical Investigation 2006, 116: 3252-3257. PMID: 17099776, PMCID: PMC1635165, DOI: 10.1172/jci29251.Peer-Reviewed Original ResearchConceptsIL-10 secretionTr1 regulatory T cellsRegulatory T cellsHuman autoimmune diseasesMultiple sclerosisT cellsAutoimmune diseasesTr1 cellsIL-10Antiinflammatory cytokine IL-10Cytokine IL-10IFN-gamma secretionT cell functionT cell activationHuman T cellsTreg defectsTreg phenotypeTreg functionCostimulatory moleculesHealthy subjectsMurine modelCD46 costimulationCell activationCD28 costimulationPatientsOR.9. Il-10 Plays a Contrasting Role in Suppression By Functionally Distinct, Dr+ and Dr− Human Natural Regulatory T-Cells
Baecher-Allan C, Ashley C, Hafler D. OR.9. Il-10 Plays a Contrasting Role in Suppression By Functionally Distinct, Dr+ and Dr− Human Natural Regulatory T-Cells. Clinical Immunology 2006, 119: s7. DOI: 10.1016/j.clim.2006.04.011.Peer-Reviewed Original Research
2004
Human CD4+CD25+ regulatory T cells
Baecher-Allan C, Viglietta V, Hafler DA. Human CD4+CD25+ regulatory T cells. Seminars In Immunology 2004, 16: 89-98. PMID: 15036232, DOI: 10.1016/j.smim.2003.12.005.Peer-Reviewed Original ResearchConceptsRegulatory T cellsT reg cellsT cellsT reg populationT cell subsetsT-reg functionHuman peripheral bloodIL-10Lymph nodesPeripheral bloodCell subsetsFunctional outcomeCord bloodTCR stimuliRapid effectsCellular compositionTCR signalsPotential involvementActivation stateStrong stimulationMiceBloodDisparate findingsCellsCulture conditions
1998
Identification 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
1996
Downregulation of IL‐10 secretion and enhanced antigen‐presenting abilities following HTLV‐I infection of T cells
Scholz C, Hafler DA, Höllsberg P. Downregulation of IL‐10 secretion and enhanced antigen‐presenting abilities following HTLV‐I infection of T cells. Journal Of Neuroscience Research 1996, 45: 786-794. PMID: 8892090, DOI: 10.1002/(sici)1097-4547(19960915)45:6<786::aid-jnr15>3.0.co;2-u.Peer-Reviewed Original ResearchConceptsT cell clonesAntigen-presenting abilityHTLV-I infectionT cellsUninfected T cellsIL-10Immunosuppressive cytokine IL-10Human T-cell lymphotropic virus type ICD8 T cell proliferationMajor histocompatibility complex class IIPeripheral blood T cellsSpecific T cell clonesHistocompatibility complex class IILymphotropic virus type IGeneral immune activationHTLV-I myelopathySoluble peptide antigenCytokine IL-10IL-10 secretionEpstein-Barr virusAntigen-presenting cellsBlood T cellsInterferon-gamma secretionBest antigen-presenting cellsCytotoxic T cellsIL-12 induces human T cells secreting IL-10 with IFN-gamma.
Windhagen A, Anderson DE, Carrizosa A, Williams RE, Hafler DA. IL-12 induces human T cells secreting IL-10 with IFN-gamma. The Journal Of Immunology 1996, 157: 1127-31. PMID: 8757617, DOI: 10.4049/jimmunol.157.3.1127.Peer-Reviewed Original ResearchConceptsIL-10T cell responsesIL-12T cell clonesIFN-gammaT cellsT cell linesHuman T cellsMyelin basic protein-reactive T cell clonesCell responsesPredominant T cell responseShort-term T cell linesConcomitant secretionHuman T cell responsesCell clonesAg-specific stimulationIFN-gamma secretionIFN-gamma productionAnti-CD3 mAbCell linesMyelin basic proteinGamma AbIL-2IL-4Cytokine secretion
1995
Modulation of cytokine patterns of human autoreactive T cell clones by a single amino acid substitution of their peptide ligand
Windhagen A, Schooz C, Höllsberg P, Fukaura H, Sette A, Hafler D. Modulation of cytokine patterns of human autoreactive T cell clones by a single amino acid substitution of their peptide ligand. Immunity 1995, 2: 373-380. PMID: 7536622, DOI: 10.1016/1074-7613(95)90145-0.Peer-Reviewed Original ResearchConceptsT cell clonesCytokine patternCell clonesHuman autoreactive T cell clonesT cell cytokine secretionAutoreactive T cell clonesT cell receptor contact residuesIL-4 secretionAltered peptide ligandMajor histocompatability complexPresence of ionomycinMyelin basic proteinIL-10Receptor contact residuesIL-4IL-2TCR antagonistsCytokine secretionImmune responseIFN-gammaPeptide ligandsProtein secretionCalcium fluxMature T-cell clonesSecretion