2022
Type I interferon transcriptional network regulates expression of coinhibitory receptors in human T cells
Sumida TS, Dulberg S, Schupp JC, Lincoln MR, Stillwell HA, Axisa PP, Comi M, Unterman A, Kaminski N, Madi A, Kuchroo VK, Hafler DA. Type I interferon transcriptional network regulates expression of coinhibitory receptors in human T cells. Nature Immunology 2022, 23: 632-642. PMID: 35301508, PMCID: PMC8989655, DOI: 10.1038/s41590-022-01152-y.Peer-Reviewed Original ResearchConceptsCoinhibitory receptor expressionHuman T cellsIFN-I responsesCoinhibitory receptorsT cellsTIGIT expressionReceptor expressionAcute SARS-CoV-2 infectionPD-1/TimSARS-CoV-2 infectionEnhancement of immunotherapyType 1 interferonT-cell featuresLAG-3Infectious diseasesDifferent temporal kineticsTranscription factorsCancer therapyReceptorsCell featuresKey transcription factorIFNPresent studyMRNA profilingKey regulator
2013
The CD226/CD155 Interaction Regulates the Proinflammatory (Th1/Th17)/Anti-Inflammatory (Th2) Balance in Humans
Lozano E, Joller N, Cao Y, Kuchroo VK, Hafler DA. The CD226/CD155 Interaction Regulates the Proinflammatory (Th1/Th17)/Anti-Inflammatory (Th2) Balance in Humans. The Journal Of Immunology 2013, 191: 3673-3680. PMID: 23980210, PMCID: PMC3819731, DOI: 10.4049/jimmunol.1300945.Peer-Reviewed Original ResearchConceptsNaive T cellsT cellsInflammatory balanceIL-13IL-17-producing cellsRole of CD226IL-17 productionIL-17 secretionHuman autoimmune diseasesIFN-γ productionIL-13 secretionIFN-γ expressionProduction of IFNSTAT-6 phosphorylationT cell activationHuman T cellsLigand CD155Th17 cellsIL-17Autoimmune diseasesIL-4T-betTh1 differentiationTh17 conditionsTherapeutic approaches
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 costimulationPatientsDysregulated T cell expression of TIM3 in multiple sclerosis
Koguchi K, Anderson DE, Yang L, O'Connor KC, Kuchroo VK, Hafler DA. Dysregulated T cell expression of TIM3 in multiple sclerosis. Journal Of Experimental Medicine 2006, 203: 1413-1418. PMID: 16754722, PMCID: PMC2118310, DOI: 10.1084/jem.20060210.Peer-Reviewed Original ResearchConceptsIFN-gamma secretionCSF clonesT cell expressionMultiple sclerosisT cellsHuman T cellsTIM3 expressionControl subjectsCerebrospinal fluidCell expressionMucin-domain-containing moleculesPathogenesis of MSEx vivo CD4Human autoimmune diseasesT helper cellsT-cell immunoglobulinT cell clonesVivo CD4Costimulatory blockadeTh1 responseCytokine profileCell surface moleculesAutoimmune diseasesHelper cellsInterleukin-12
2000
A novel population of B7‐1+ T cells producing intracellular IL‐4 is decreased in patients with multiple sclerosis
Kipp B, Bar‐Or A, Gausling R, Oliveira E, Fruhan S, Stuart W, Hafler D. A novel population of B7‐1+ T cells producing intracellular IL‐4 is decreased in patients with multiple sclerosis. European Journal Of Immunology 2000, 30: 2092-2100. PMID: 10940899, DOI: 10.1002/1521-4141(200007)30:7<2092::aid-immu2092>3.0.co;2-7.Peer-Reviewed Original ResearchConceptsT cell receptorIntracellular IL-4Multiple sclerosisT cellsB7-1IL-4Autoimmune diseasesTNF-alphaIFN-gammaIL-4-producing T cellsLittle IL-4Immunoregulatory T cellsIL-4 productionIntracellular IFN-gammaT cell populationsLittle IFN-gammaNovel populationDiverse TCR repertoireMHC class IIHuman T cellsShort-term cultureCell surface moleculesTCR repertoireNormal subjectsPatientsParadoxical inhibition of T-cell function in response to CTLA-4 blockade; heterogeneity within the human T-cell population
Anderson D, Bieganowska K, Bar-Or A, Oliveira E, Carreno B, Collins M, Hafler D. Paradoxical inhibition of T-cell function in response to CTLA-4 blockade; heterogeneity within the human T-cell population. Nature Medicine 2000, 6: 211-214. PMID: 10655112, DOI: 10.1038/72323.Peer-Reviewed Original ResearchConceptsCTLA-4 blockadeT cell populationsCTLA-4T cellsMonoclonal antibodiesB7-1B7-2Immune responseCytotoxic T-lymphocyte antigen-4Whole T cell populationsT-lymphocyte antigen-4Antigen-specific T cellsT cell activation stateHuman T cell populationsT cell functionT cell receptor signalsCo-stimulatory signalsDifferent T cellsT cell stimulationEffect of B7T cell activationActivation stateT cell receptorHuman T cellsFab fragments
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
1997
Expression of a hypoglycosylated form of CD86 (B7-2) on human T cells with altered binding properties to CD28 and CTLA-4.
Höllsberg P, Scholz C, Anderson DE, Greenfield EA, Kuchroo VK, Freeman GJ, Hafler DA. Expression of a hypoglycosylated form of CD86 (B7-2) on human T cells with altered binding properties to CD28 and CTLA-4. The Journal Of Immunology 1997, 159: 4799-805. PMID: 9366404, DOI: 10.4049/jimmunol.159.10.4799.Peer-Reviewed Original ResearchMeSH KeywordsAbataceptAnimalsAntibodies, MonoclonalAntigens, CDAntigens, DifferentiationB7-2 AntigenCD28 AntigensCD3 ComplexCD4-Positive T-LymphocytesCell Line, TransformedCHO CellsClone CellsCricetinaeCTLA-4 AntigenGlycosylationHumansImmunoconjugatesLymphocyte ActivationMembrane GlycoproteinsProtein BindingT-Lymphocyte SubsetsConceptsPost-translational modificationsCell type-specific post-translational modificationsHuman T cellsDifferent cell typesMajor costimulatory signalChinese hamster ovary cellsHamster ovary cellsCell clonesFusion proteinCostimulatory signalsCell typesT cell activationFunctional significanceOvary cellsBiochemical analysisSurface membraneCostimulatory functionDetectable bindingExpressionT cellsClonesCell activationCTLA-4-Ig fusion proteinCellsCell expression
1996
IL-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
1994
Clonal expansion and persistence of human T cells specific for an immunodominant myelin basic protein peptide.
Wucherpfennig KW, Zhang J, Witek C, Matsui M, Modabber Y, Ota K, Hafler DA. Clonal expansion and persistence of human T cells specific for an immunodominant myelin basic protein peptide. The Journal Of Immunology 1994, 152: 5581-92. PMID: 7514641, DOI: 10.4049/jimmunol.152.11.5581.Peer-Reviewed Original ResearchConceptsT cellsNormal subjectsImmunodominant myelin basic protein peptideMBP-specific T cell linesDR2 haplotypeSpecific T cell clonesTCR beta-chain sequencesReactive T cellsT cell responsesHLA-DR moleculesT cell clonesIdentical TCR sequencesMyelin basic protein peptideIL-2 stimulationT cell linesHuman T cellsAlpha-chain rearrangementMyelin basic proteinMultiple sclerosisBeta chain sequencesTCR rearrangementsPatientsCell responsesTCR alphaTCR sequencesT cell anergy
Lasalle J, Hafler D. T cell anergy. The FASEB Journal 1994, 8: 601-608. PMID: 8005388, DOI: 10.1096/fasebj.8.9.8005388.Peer-Reviewed Original ResearchConceptsImmunologic self toleranceAutoreactive T cellsT cell anergyMHC class IIT cellsClonal anergyT cell presentationT cell clonal anergySelf antigensCell anergySelf toleranceCell presentationClass IIAutologous T cellsAbsence of costimulationHuman T cellsSecondary unresponsivenessHigh extracellular concentrationsAntigenic stimulationAntigen presentationAntigen resultsAnergyPrimary proliferationPeptide antigensAntigen
1991
Presentation of autoantigen by human T cells.
LaSalle JM, Ota K, Hafler DA. Presentation of autoantigen by human T cells. The Journal Of Immunology 1991, 147: 774-80. PMID: 1713605, DOI: 10.4049/jimmunol.147.3.774.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAntigens, CDAntigens, Differentiation, T-LymphocyteAntigens, SurfaceAutoantigensCD2 AntigensCD58 AntigensEpitopesHistocompatibility AntigensHLA-D AntigensHumansIntegrin beta1Leukocyte Common AntigensLymphocyte ActivationLymphocyte Function-Associated Antigen-1Membrane GlycoproteinsMolecular Sequence DataMyelin Basic ProteinReceptors, ImmunologicT-LymphocytesConceptsT cell clonesMBP-reactive T cell clonesAutologous T cellsMyelin basic proteinMHC class IIT cellsHuman T cellsCell clonesAdhesion molecules LFA-3Class IIReactive T cell clonesWhole myelin basic proteinPresentation of autoantigensT cell interactionsActivated T cellsT cell presentationTCR-mediated responsesAg preparationsImmune responseMHC classSelf-AgForeign AgsInflammatory sitesCell presentationLFA-3
1989
Lymphokine regulation of CD45R expression on human T cell clones.
Brod SA, Rudd CE, Purvee M, Hafler DA. Lymphokine regulation of CD45R expression on human T cell clones. Journal Of Experimental Medicine 1989, 170: 2147-2152. PMID: 2531196, PMCID: PMC2189525, DOI: 10.1084/jem.170.6.2147.Peer-Reviewed Original ResearchConceptsHigh molecular weight isoformsMolecular weight isoformsSingle cell cloningDifferent lineagesCell lineagesCell clonesT-cell lineageWeight isoformsCell cloningHuman T cellsActivated T cellsLineagesExpressionDifferential pathwaysCytokines IL-1IsoformsClonesT cellsCellsRegulationLymphokine regulationCell expressionT cell clonesIL-1Cloning