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 availability
2020
Transcriptomic and clonal characterization of T cells in the human central nervous system
Pappalardo JL, Zhang L, Pecsok MK, Perlman K, Zografou C, Raddassi K, Abulaban A, Krishnaswamy S, Antel J, van Dijk D, Hafler DA. Transcriptomic and clonal characterization of T cells in the human central nervous system. Science Immunology 2020, 5 PMID: 32948672, PMCID: PMC8567322, DOI: 10.1126/sciimmunol.abb8786.Peer-Reviewed Original ResearchConceptsCentral nervous systemCSF of patientsT cellsCerebrospinal fluidMultiple sclerosisImmune surveillanceNervous systemCSF T cellsHuman central nervous systemHealthy human donorsT cell activationImmune dysfunctionNeuroinflammatory diseasesCytotoxic capacityHealthy donorsHealthy individualsCell activationHuman donorsTissue adaptationPatientsClonal characterizationExpression of genesCellsSurveillanceFurther characterization
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 signals
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
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
1998
Expansion of autoreactive T cells in multiple sclerosis is independent of exogenous B7 costimulation.
Scholz C, Patton K, Anderson D, Freeman G, Hafler D. Expansion of autoreactive T cells in multiple sclerosis is independent of exogenous B7 costimulation. The Journal Of Immunology 1998, 160: 1532-8. PMID: 9570577, DOI: 10.4049/jimmunol.160.3.1532.Peer-Reviewed Original ResearchMeSH KeywordsAbataceptAntigens, CDAntigens, DifferentiationAutoantigensB7-1 AntigenB7-2 AntigenClone CellsCTLA-4 AntigenEpitopes, T-LymphocyteHumansImmunoconjugatesImmunoglobulin Fc FragmentsImmunosuppressive AgentsInterleukin-4Lymphocyte ActivationMembrane GlycoproteinsMultiple SclerosisMyelin Basic ProteinRecombinant Fusion ProteinsT-Lymphocyte SubsetsTetanus ToxoidThymidineConceptsCD4 T cellsMultiple sclerosisT cellsB7-1Myelin basic proteinPathogenesis of MSMyelin-reactive T cellsPeripheral blood T cellsB7-2 engagementAutoreactive T cellsBlood T cellsAbsence of costimulationCentral nervous systemAntigen-specific signalT cell activationMS patientsB7 costimulationInflammatory diseasesTetanus toxoidB7-2Normal controlsNormal subjectsCostimulatory signalsNervous systemCell activation
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
1994
Human T cell lymphotropic virus type I-induced T cell activation. Resistance to TGF-beta 1-induced suppression.
Höllsberg P, Ausubel LJ, Hafler DA. Human T cell lymphotropic virus type I-induced T cell activation. Resistance to TGF-beta 1-induced suppression. The Journal Of Immunology 1994, 153: 566-73. PMID: 8021495, DOI: 10.4049/jimmunol.153.2.566.Peer-Reviewed Original ResearchConceptsT cell clonesT cell activationHuman T-cell lymphotropic virus type ILymphotropic virus type IVirus type ICell activationCell clonesT cellsCD3/TCR complexHTLV-I myelopathyT cell proliferationType IImmune regulationHTLVHyperphosphorylation of pRbProductive infectionCell cycle progressionCell proliferationTCR complexPatientsG1 phaseInfectionSingle cell cloningCycle progressionActivation
1992
CTLA-4 and CD28 mRNA are coexpressed in most T cells after activation. Expression of CTLA-4 and CD28 mRNA does not correlate with the pattern of lymphokine production.
Freeman GJ, Lombard DB, Gimmi CD, Brod SA, Lee K, Laning JC, Hafler DA, Dorf ME, Gray GS, Reiser H. CTLA-4 and CD28 mRNA are coexpressed in most T cells after activation. Expression of CTLA-4 and CD28 mRNA does not correlate with the pattern of lymphokine production. The Journal Of Immunology 1992, 149: 3795-801. PMID: 1281186, DOI: 10.4049/jimmunol.149.12.3795.Peer-Reviewed Original ResearchMeSH KeywordsAbataceptAnimalsAntigens, CDAntigens, DifferentiationAntigens, Differentiation, T-LymphocyteAntigens, SurfaceB7-1 AntigenBase SequenceBlotting, NorthernCD28 AntigensCell Adhesion MoleculesCell LineCTLA-4 AntigenHumansImmunoconjugatesInterferon-gammaInterleukinsLeukemia, T-CellLymphocyte ActivationLymphokinesMiceMolecular Sequence DataOligonucleotide ProbesPolymerase Chain ReactionRNA, MessengerT-LymphocytesTumor Necrosis Factor-alphaConceptsT cell clonesCTLA-4 mRNACTLA-4T cellsActivated T cellsT cell activationT cell linesMurine T cell clonesCell clonesCD28 mRNACostimulatory signalsT cell receptor-dependent stimulationCell activationNormal T cell subsetsAg-presenting cellsHuman T cell clonesT cell subsetsExpression of CD28Th2 cytokine profileMost T cellsLeukemic T cell lineCell linesReceptor-dependent stimulationSuch costimulatory signalsInteraction of B7Characterization of HTLV-I in vivo infected T cell clones. IL-2-independent growth of nontransformed T cells.
Höllsberg P, Wucherpfennig KW, Ausubel LJ, Calvo V, Bierer BE, Hafler DA. Characterization of HTLV-I in vivo infected T cell clones. IL-2-independent growth of nontransformed T cells. The Journal Of Immunology 1992, 148: 3256-63. PMID: 1374452, DOI: 10.4049/jimmunol.148.10.3256.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntigens, Differentiation, T-LymphocyteBase SequenceCD3 ComplexClone CellsCyclosporineHTLV-I InfectionsHumansInterleukin-2Lymphocyte ActivationMolecular Sequence DataPolyenesReceptors, Antigen, T-CellReceptors, Interleukin-2RNA, MessengerSirolimusT-LymphocytesTacrolimusConceptsT cell clonesClonal proliferationCell clonesIL-2 receptor signalLymphotrophic virus type ICharacterization of HTLVInfected T cell clonesHTLV-I provirusBlood of subjectsVirus type IT cell activationAbsence of mitogensIL-2-mediated signalingIL-2-independent growthSite of actionMononuclear cellsIL-2Polymerase chain reactionT cellsExogenous growth factorsPeriodic restimulationFK-506Cell activationHTLVP55 chain
1990
T‐T cell interactions are mediated by adhesion molecules
Brod S, Purvee M, Benjamin D, Hafler D. T‐T cell interactions are mediated by adhesion molecules. European Journal Of Immunology 1990, 20: 2259-2268. PMID: 1700751, DOI: 10.1002/eji.1830201015.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntigens, Differentiation, T-LymphocyteAntigens, SurfaceCD3 ComplexCD58 AntigensCell Adhesion MoleculesCell CommunicationClone CellsHumansImmunophenotypingInterleukin-2Lymphocyte ActivationLymphocyte Function-Associated Antigen-1Membrane GlycoproteinsMitogensReceptors, Antigen, T-CellT-LymphocytesConceptsT cell clonesAutologous T cell clonesPeripheral blood T cellsAdhesion molecules LFA-1Blood T cellsT cellsLFA-3Major histocompatibility complexInflammatory responseCell clonesICAM-1LFA-1T cell immune functionCD3/T cell receptor complexSpecific T cellsCell adhesion molecules LFA-1Cell immune functionT cell interactionsT cell activationT cell receptor complexMHC determinantsCell receptor complexImmune functionCell activationCD2 pathway
1989
Mechanisms of immune memory. T cell activation and CD3 phosphorylation correlates with Ta1 (CDw26) expression.
Hafler DA, Chofflon M, Benjamin D, Dang NH, Breitmeyer J. Mechanisms of immune memory. T cell activation and CD3 phosphorylation correlates with Ta1 (CDw26) expression. The Journal Of Immunology 1989, 142: 2590-6. PMID: 2564857, DOI: 10.4049/jimmunol.142.8.2590.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, Differentiation, T-LymphocyteAntigens, SurfaceCalciumCD2 AntigensCD3 ComplexHumansImmunologic MemoryLymphocyte ActivationPhosphorylationProtein Kinase CReceptors, Antigen, T-CellReceptors, ImmunologicT-LymphocytesTetradecanoylphorbol AcetateTumor Necrosis Factor Receptor Superfamily, Member 7ConceptsT cell immune memoryT cell activationImmune memoryT cellsCell activationPeripheral blood T cellsTA1 expressionBlood T cellsIntracellular calcium levelsTA1 cellsCD3/TCRT cell linesCalcium ionophore ionomycinAg challengeIL-2T lymphocytesMitogenic antibodiesCalcium levelsPhorbol ester PMAIonophore ionomycinCD2 moleculeGrowth factorActivation requirementsInvariant chainCD2 stimulation
1988
Regulation of T cell clone function via CD4 and CD8 molecules. Anti-CD4 can mediate two distinct inhibitory activities.
Blue ML, Hafler DA, Daley JF, Levine H, Craig KA, Breitmeyer JB, Schlossman SF. Regulation of T cell clone function via CD4 and CD8 molecules. Anti-CD4 can mediate two distinct inhibitory activities. The Journal Of Immunology 1988, 140: 376-83. PMID: 2891768, DOI: 10.4049/jimmunol.140.2.376.Peer-Reviewed Original ResearchConceptsReceptor functionAnti-CD4Anti-CD8 monoclonal antibodiesCD3-TiCell receptor functionMajor histocompatibility complex moleculesIntracellular free Ca2CD3 T-cell receptorT cell activationHistocompatibility complex moleculesCytotoxic functionT cell receptor functionCD8 moleculesCD4CD8Distinct inhibitory activityCD4 moleculeCell activationAntigen receptor functionCell receptorMonoclonal antibodiesFree Ca2Dependent proliferationFunctional effectsSoluble antibodies
1987
Phosphorylation of CD4 and CD8 molecules following T cell triggering.
Blue ML, Hafler DA, Craig KA, Levine H, Schlossman SF. Phosphorylation of CD4 and CD8 molecules following T cell triggering. The Journal Of Immunology 1987, 139: 3949-54. PMID: 2961801, DOI: 10.4049/jimmunol.139.12.3949.Peer-Reviewed Original ResearchConceptsCell receptor complexCD3-T cell receptor complexT cell triggeringReceptor complexPhorbol myristate acetate (PMA) treatmentMolecular signaling mechanismsDifferent receptor pathwaysErythrocyte binding proteinCD8 moleculesSignaling mechanismBinding proteinPhosphorylationCell triggeringT cell activationCD2 pathwayT cellsReceptor pathwayMolecular modificationsT cell clonesCell activationCell clonesPathwayActivationCD4Cells