2023
BSBM-18 SINGLE-CELL PROFILING TUMOR-INFILTRATING IMMUNE CELLS REVEALS CXCL13+ FOLLICULAR HELPER-LIKE CD4+ T CELLS IN HUMAN BRAIN TUMORS
Lu B, Lucca L, DiStasio M, Liu Y, Pham G, Buitrago-Pocasangre N, Arnal-Estape A, Moliterno J, Chiang V, Omuro A, Hafler D. BSBM-18 SINGLE-CELL PROFILING TUMOR-INFILTRATING IMMUNE CELLS REVEALS CXCL13+ FOLLICULAR HELPER-LIKE CD4+ T CELLS IN HUMAN BRAIN TUMORS. Neuro-Oncology Advances 2023, 5: iii4-iii4. PMCID: PMC10402449, DOI: 10.1093/noajnl/vdad070.014.Peer-Reviewed Original ResearchT cell populationsT cell functionT cellsHigh-grade gliomasBrain metastasesHuman brain tumorsImmune cellsBrain tumorsNon-small cell lung cancer brain metastasesB cellsAnti-PD-1 therapy responseCell lung cancer brain metastasesLung cancer brain metastasesProductive antitumor immune responsesFollicular helper T cellsT-cell receptor sequencingTumor-infiltrating T cellsAntitumor T-cell functionCancer brain metastasesCo-inhibitory receptorsAntitumor immune responseCell receptor sequencingLonger overall survivalCell functionTertiary lymphoid structures
2022
Fatty Acid Metabolism and T Cells in Multiple Sclerosis
Pompura SL, Hafler DA, Dominguez-Villar M. Fatty Acid Metabolism and T Cells in Multiple Sclerosis. Frontiers In Immunology 2022, 13: 869197. PMID: 35603182, PMCID: PMC9116144, DOI: 10.3389/fimmu.2022.869197.Peer-Reviewed Original ResearchConceptsT cell functionT cellsMultiple sclerosisSpecific lipid speciesEffector T cellsRegulatory T cellsCell functionT helper subsetsMetabolic programsT cell activationT cell transitionLipid speciesFatty acid metabolismTh subsetsHelper subsetsEffector stateBody of evidenceCell activationDisease settingsDisease statesFunctional phenotypeOrganismal levelAcid metabolismMetabolic remodelingNutrient availabilityTCR-sequencing in cancer and autoimmunity: barcodes and beyond
Pauken KE, Lagattuta KA, Lu BY, Lucca LE, Daud AI, Hafler DA, Kluger HM, Raychaudhuri S, Sharpe AH. TCR-sequencing in cancer and autoimmunity: barcodes and beyond. Trends In Immunology 2022, 43: 180-194. PMID: 35090787, PMCID: PMC8882139, DOI: 10.1016/j.it.2022.01.002.Peer-Reviewed Original ResearchConceptsT cell receptorT cellsMolecular barcodesProgrammed Death-1 BlockadeTCR sequencesDeath-1 blockadeUnique TCR sequencesNaïve T cellsT cell functionCell divisionMolecular phenotypesBarcodesImmune responseAntigen specificitySingle cellsCell receptorCell functionRecent technological advancesCancerTCR dataCells
2021
The double-edged sword: Harnessing PD-1 blockade in tumor and autoimmunity
Kuchroo JR, Hafler DA, Sharpe AH, Lucca LE. The double-edged sword: Harnessing PD-1 blockade in tumor and autoimmunity. Science Immunology 2021, 6: eabf4034. PMID: 34739340, DOI: 10.1126/sciimmunol.abf4034.Peer-Reviewed Original ResearchConceptsImmune-related adverse eventsPD-1 blockadeRegulatory T cell functionImmune checkpoint blockadeCheckpoint blockade immunotherapyT cell responsesT cell functionBlockade immunotherapyAdverse eventsAntitumor immunityCheckpoint blockadeCell responsesBlockadeCell functionAutoimmunityMechanistic featuresEdged swordImmunotherapyTumorsCancerImmunityCirculating clonally expanded T cells reflect functions of tumor-infiltrating T cells
Lucca LE, Axisa PP, Lu B, Harnett B, Jessel S, Zhang L, Raddassi K, Zhang L, Olino K, Clune J, Singer M, Kluger HM, Hafler DA. Circulating clonally expanded T cells reflect functions of tumor-infiltrating T cells. Journal Of Experimental Medicine 2021, 218: e20200921. PMID: 33651881, PMCID: PMC7933991, DOI: 10.1084/jem.20200921.Peer-Reviewed Original ResearchConceptsTumor-infiltrating T cellsT cellsUnique transcriptional patternsFeatures of exhaustionLongitudinal immune monitoringPeripheral immune environmentsT cell responsesT cell functionSingle-cell levelTranscriptional patternsTCR sharingTerminal exhaustionImmune environmentImmune monitoringCancer immunotherapyMetastatic melanomaEffector functionsCell responsesTumor tissueGene signatureTumorsCell functionImmunotherapyTCRαβBlood
2016
The Link Between CD6 and Autoimmunity: Genetic and Cellular Associations.
Kofler DM, Farkas A, von Bergwelt-Baildon M, Hafler DA. The Link Between CD6 and Autoimmunity: Genetic and Cellular Associations. Current Drug Targets 2016, 17: 651-65. PMID: 26844569, DOI: 10.2174/1389450117666160201105934.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDAntigens, Differentiation, T-LymphocyteArthritis, RheumatoidAutoimmunityCD4-Positive T-LymphocytesCell Adhesion Molecules, NeuronalClinical Trials as TopicDisease Models, AnimalFetal ProteinsGenetic Predisposition to DiseaseHumansMultiple SclerosisPolymorphism, Single NucleotideConceptsMultiple sclerosisRheumatoid arthritisCentral nervous systemNervous systemSingle nucleotide polymorphismsDevelopment of MSTreatment of RARole of CD6T cell traffickingT cell functionGenetic risk factorsEndothelial cell barrierCD6 geneClinical responseGenetic associationClinical featuresAutoimmune diseasesSynovial cellsRisk factorsTumor necrosisSynovial fibroblastsPossible common mechanismT cellsT lymphocytesLeukocyte trafficking
2012
Prostaglandin E2 Affects T Cell Responses through Modulation of CD46 Expression
Kickler K, Maltby K, Choileain S, Stephen J, Wright S, Hafler DA, Jabbour HN, Astier AL. Prostaglandin E2 Affects T Cell Responses through Modulation of CD46 Expression. The Journal Of Immunology 2012, 188: 5303-5310. PMID: 22544928, PMCID: PMC3758685, DOI: 10.4049/jimmunol.1103090.Peer-Reviewed Original ResearchConceptsG protein-coupled receptor kinasesCell functionProtein-coupled receptor kinasesT cell functionT cell activationG protein-coupled receptorsProtein-coupled receptorsCD46 expressionPrimary T cellsReceptor kinaseT cellsCD46 functionsCell activationRegulatory mechanismsDiverse rolesDifferentiation pathwayNovel roleCytokine productionProstanoid familyActivation signalsActivated T cellsT cell responsesChronic inflammatory diseaseSubtypes of receptorsCD46 activationProstaglandin E2 affects T cell responses through modulation of CD46 expression. (178.8)
Astier A, Kickler K, Ni Choileain S, Stephen J, Hafler D, Jabbour H. Prostaglandin E2 affects T cell responses through modulation of CD46 expression. (178.8). The Journal Of Immunology 2012, 188: 178.8-178.8. DOI: 10.4049/jimmunol.188.supp.178.8.Peer-Reviewed Original ResearchT cell functionCell functionReceptor kinase familyT cell activationProstaglandin E2CD46 expressionT cellsPrimary T cellsKinase familyCytokine productionCD46 functionsCell activationRegulatory mechanismsDiverse rolesDifferentiation pathwayNovel roleG proteinsCell surfaceRole of PGE2Addition of PGE2T cell surfaceT cell responsesChronic inflammatory diseaseComplement regulator CD46Activation signalsThe TIGIT/CD226 Axis Regulates Human T Cell Function
Lozano E, Dominguez-Villar M, Kuchroo V, Hafler DA. The TIGIT/CD226 Axis Regulates Human T Cell Function. The Journal Of Immunology 2012, 188: 3869-3875. PMID: 22427644, PMCID: PMC3324669, DOI: 10.4049/jimmunol.1103627.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntigens, Differentiation, T-LymphocyteCD4-Positive T-LymphocytesCell CommunicationCell ProliferationCells, CulturedCytokinesDendritic CellsGATA3 Transcription FactorGene Expression RegulationHumansImmune ToleranceReceptors, ImmunologicReceptors, VirusRNA, Small InterferingSignal TransductionT-Box Domain ProteinsConceptsT cell functionT cellsAutoimmune diseasesT-betTIGIT/CD226 axisHuman T cell responsesT cell-intrinsic mannerHuman T cell functionAlternative costimulatory pathwaysT cell responsesCell functionDendritic cell surfaceHuman autoimmune diseasesIL-10 expressionT cell IgIFN regulatory factor 4T cell proliferationOrphan receptor CDirect inhibitory effectIFN-γ mRNACell-intrinsic mannerRegulatory factor 4TIGIT expressionTIGIT knockdownTolerogenic phenotype
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 factorT-Cells in Multiple Sclerosis
Severson C, Hafler DA. T-Cells in Multiple Sclerosis. 2009, 51: 1-24. PMID: 19582415, DOI: 10.1007/400_2009_12.Peer-Reviewed Original ResearchConceptsMultiple sclerosisT cellsMultifocal demyelinating diseaseMultiple cell subtypesRegulatory T cellsT cell subsetsT cell functionCentral nervous systemRational therapeutic strategiesT cell activationDemyelinating diseaseMS pathogenesisMS pathophysiologyCell subsetsAdaptive immunityEffective treatmentTherapeutic strategiesNervous systemCell activationCell subtypesEvidence implicateSpecific toleranceFunctional defectsIntrinsic cellsCell functionT-Cells in Multiple Sclerosis
Severson C, Hafler D. T-Cells in Multiple Sclerosis. Results And Problems In Cell Differentiation 2009, 51: 75-98. DOI: 10.1007/400_2009_9012.Peer-Reviewed Original ResearchMultiple sclerosisT cellsMultifocal demyelinating diseaseMultiple cell subtypesRegulatory T cellsT cell subsetsT cell functionCentral nervous systemRational therapeutic strategiesT cell activationDemyelinating diseaseMS pathogenesisMS pathophysiologyCell subsetsAdaptive immunityEffective treatmentTherapeutic strategiesNervous systemCell activationCell subtypesEvidence implicateSpecific toleranceFunctional defectsIntrinsic cellsCell function
2008
Lack of TIM-3 Immunoregulation in Multiple Sclerosis
Yang L, Anderson DE, Kuchroo J, Hafler DA. Lack of TIM-3 Immunoregulation in Multiple Sclerosis. The Journal Of Immunology 2008, 180: 4409-4414. PMID: 18354161, DOI: 10.4049/jimmunol.180.7.4409.Peer-Reviewed Original ResearchConceptsMultiple sclerosisT cell functionTim-3Untreated patientsTreatment of MSType 1 Th cellsBlocking Tim-3Tim-3 functionTim-3 regulationT-cell infiltratesTim-3 expressionPeripheral immune systemCell functionHuman autoimmune diseasesIFN-gamma secretionCNS white matterT cell stimulationHuman Tim-3Cell infiltrateGlatiramer acetateImmune toleranceAutoimmune diseasesControl subjectsTh cellsInflammatory diseases
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 costimulationPatients
2004
Loss of Functional Suppression by CD4+CD25+ Regulatory T Cells in Patients with Multiple Sclerosis
Viglietta V, Baecher-Allan C, Weiner HL, Hafler DA. Loss of Functional Suppression by CD4+CD25+ Regulatory T Cells in Patients with Multiple Sclerosis. Journal Of Experimental Medicine 2004, 199: 971-979. PMID: 15067033, PMCID: PMC2211881, DOI: 10.1084/jem.20031579.Peer-Reviewed Original ResearchConceptsRegulatory T cellsMultiple sclerosisT cellsRegulatory T cell functionActivity of murineSpontaneous autoimmune diseaseT cell functionSingle cell cloning experimentsPeripheral toleranceCell cloning experimentsAutoimmune diseasesPeripheral bloodInflammatory diseasesHealthy donorsHuman CD4Effector functionsNormal controlsPatientsFunctional suppressionCell functionSignificant decreaseSclerosisProtein peptidesDiseaseActive suppression
2003
Allelic Variation of MHC Structure Alters Peptide Ligands to Induce Atypical Partial Agonistic CD8+ T Cell Function
Lim DG, Slavik JM, Bourcier K, Smith KJ, Hafler DA. Allelic Variation of MHC Structure Alters Peptide Ligands to Induce Atypical Partial Agonistic CD8+ T Cell Function. Journal Of Experimental Medicine 2003, 198: 99-109. PMID: 12847139, PMCID: PMC2196091, DOI: 10.1084/jem.20021796.Peer-Reviewed Original ResearchConceptsT cell functionT cell clonesCell functionReactive T cell clonesCell clonesT cell responsesDifferent T cell responsesIndividual T cell clonesHLA-A2 moleculesAltered peptide ligandHLA-A2 peptideRecognition of MHCT cell receptorMHC-peptide complexesPolymorphic amino acidsFunctional outcomeHLA-A2Peptide ligandsAgonist functionMHC moleculesCell responsesEarly intracellularLong-term expressionCell receptorAntigen recognition
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
2000
Examination of CD8+ T Cell Function in Humans Using MHC Class I Tetramers: Similar Cytotoxicity but Variable Proliferation and Cytokine Production Among Different Clonal CD8+ T Cells Specific to a Single Viral Epitope
Lim D, Bourcier K, Freeman G, Hafler D. Examination of CD8+ T Cell Function in Humans Using MHC Class I Tetramers: Similar Cytotoxicity but Variable Proliferation and Cytokine Production Among Different Clonal CD8+ T Cells Specific to a Single Viral Epitope. The Journal Of Immunology 2000, 165: 6214-6220. PMID: 11086055, DOI: 10.4049/jimmunol.165.11.6214.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, ViralB7-1 AntigenCD58 AntigensCD8-Positive T-LymphocytesCell Line, TransformedClone CellsCytokinesCytotoxicity, ImmunologicDose-Response Relationship, ImmunologicEpitopes, T-LymphocyteGene Products, taxGenes, T-Cell Receptor betaHLA-A2 AntigenHuman T-lymphotropic virus 1HumansLymphocyte ActivationPeptide FragmentsStaining and LabelingConceptsT cell clonesCytokine secretionT cellsEffector functionsCell clonesCostimulatory moleculesViral epitopesHuman T-cell lymphotrophic virusDifferent T cell clonesImmunodominant viral epitopesCytotoxic effector functionClonal originT cell functionSingle viral epitopeMHC class IDifferent clonal originCD2-LFA-3 interactionInduction of proliferationClonal CD8Cytokine productionPeripheral bloodCTL populationsIL-2Lymphotrophic virusProliferative responseParadoxical 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
1993
Increased Protein Kinase C Activity in Human Memory T Cells
Höllsberg P, Melinek J, Benjamin D, Hafler D. Increased Protein Kinase C Activity in Human Memory T Cells. Cellular Immunology 1993, 149: 170-179. PMID: 8099849, DOI: 10.1006/cimm.1993.1145.Peer-Reviewed Original ResearchConceptsCD26 T cellsMemory T cellsT cell populationsMemory T cell populationsT cellsT cell receptorProliferative responseCell populationsPeripheral blood T cellsHuman memory T cellsMemory T cell functionCD26 antigen expressionT-cell surface antigensPKC activityBlood T cellsT cell functionTCR/CD3 pathwayDifferentiated T cellsCell surface antigensCD26 mAbCD26- subsetAntigen challengeAntigen expressionCD26 antigenCD26 expression