2008
CTLA4Ig treatment in patients with multiple sclerosis
Viglietta V, Bourcier K, Buckle GJ, Healy B, Weiner HL, Hafler DA, Egorova S, Guttmann CR, Rusche JR, Khoury SJ. CTLA4Ig treatment in patients with multiple sclerosis. Neurology 2008, 71: 917-924. PMID: 18794494, DOI: 10.1212/01.wnl.0000325915.00112.61.Peer-Reviewed Original ResearchConceptsMultiple sclerosisCostimulatory pathwayPhase 1 dose-escalation studyT cell-mediated autoimmune diseaseCell-mediated autoimmune diseaseRelapsing-remitting multiple sclerosisT-cell costimulatory pathwaysCostimulatory molecule interactionsMonths of infusionDose-escalation studyInterferon-gamma productionT cell activationOriginal therapeutic approachAdverse eventsImmunologic assessmentImmunologic effectsCTLA4Ig treatmentChronic inflammationAutoimmune diseasesInflammatory processT cellsImmune responseTherapeutic approachesCTLA4IgExtension study
2003
CTLA4 is associated with susceptibility to multiple sclerosis
Kantarci OH, Hebrink DD, Achenbach SJ, Atkinson EJ, Waliszewska A, Buckle G, McMurray CT, de Andrade M, Hafler DA, Weinshenker BG. CTLA4 is associated with susceptibility to multiple sclerosis. Journal Of Neuroimmunology 2003, 134: 133-141. PMID: 12507781, DOI: 10.1016/s0165-5728(02)00395-8.Peer-Reviewed Original ResearchAbataceptAge of OnsetAlternative SplicingAntigens, CDAntigens, DifferentiationBostonCTLA-4 AntigenDisease ProgressionDNA Mutational AnalysisExonsFemaleGenetic LinkageGenetic Predisposition to DiseaseGenetic TestingGenetic VariationGenotypeHaplotypesHumansImmunoconjugatesMaleMicrosatellite RepeatsMinnesotaMultiple SclerosisPolymorphism, Genetic
2002
GAD65-reactive T cells are activated in patients with autoimmune type 1a diabetes
Viglietta V, Kent SC, Orban T, Hafler DA. GAD65-reactive T cells are activated in patients with autoimmune type 1a diabetes. Journal Of Clinical Investigation 2002, 109: 895-903. PMID: 11927616, PMCID: PMC150925, DOI: 10.1172/jci14114.Peer-Reviewed Original ResearchMeSH KeywordsAbataceptAdultAntigens, CDAntigens, DifferentiationAutoimmunityB7-1 AntigenB7-2 AntigenCD28 AntigensCell DivisionCTLA-4 AntigenDiabetes Mellitus, Type 1FemaleGlutamate DecarboxylaseHumansImmunoconjugatesInterferon-gammaInterleukin-13IsoenzymesMaleMembrane GlycoproteinsSignal TransductionT-LymphocytesConceptsGAD65-reactive T cellsType 1 diabetesAutoreactive T cellsT cellsB7-1New-onset type 1 diabetesPancreatic islet cell antigensInsulin-dependent type 1 diabetesGlutamic acid decarboxylase 65B7-2 engagementType 1A diabetesMemory T cellsStimulation ex vivoIslet cell antigensB7-2 moleculesT cell proliferationB7-1 costimulationAutoimmune diseasesCTLA-4Healthy controlsPathogenic roleSelective blockadeCytokine secretionHuman diabetesT lymphocytes
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
2000
Paradoxical 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
1999
The B7–CD28/CTLA-4 costimulatory pathways in autoimmune disease of the central nervous system
Anderson D, Sharpe A, Hafler D. The B7–CD28/CTLA-4 costimulatory pathways in autoimmune disease of the central nervous system. Current Opinion In Immunology 1999, 11: 677-683. PMID: 10631554, DOI: 10.1016/s0952-7915(99)00036-9.Peer-Reviewed Original ResearchConceptsSelf-reactive T cellsB7-CD28/CTLAAutoimmune diseasesT cellsTh1/Th2 cell differentiationB7-CD28 costimulationHuman autoimmune diseasesCentral nervous systemTh2 cell differentiationCostimulatory pathwayEffector phaseCTLA-4Nervous systemCritical roleDiseaseCTLARecent studiesCell differentiationCellsPast yearPathwayAutoimmunityCD28InitiationCostimulation
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 ProteinsTetanus ToxoidThymidineT-Lymphocyte SubsetsConceptsCD4 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 expressionB7.2 expressed by T cells does not induce CD28-mediated costimulatory activity but retains CTLA4 binding: implications for induction of antitumor immunity to T cell tumors.
Greenfield EA, Howard E, Paradis T, Nguyen K, Benazzo F, McLean P, Höllsberg P, Davis G, Hafler DA, Sharpe AH, Freeman GJ, Kuchroo VK. B7.2 expressed by T cells does not induce CD28-mediated costimulatory activity but retains CTLA4 binding: implications for induction of antitumor immunity to T cell tumors. The Journal Of Immunology 1997, 158: 2025-34. PMID: 9036945, DOI: 10.4049/jimmunol.158.5.2025.Peer-Reviewed Original ResearchMeSH KeywordsAbataceptAnimalsAntigens, CDAntigens, DifferentiationB7-2 AntigenCD28 AntigensCell DivisionCTLA-4 AntigenFemaleImmunoconjugatesLymphocyte ActivationMembrane GlycoproteinsMiceMice, Inbred BALB CMice, Inbred C57BLProtein BindingThymomaThymus NeoplasmsT-LymphocytesTransfectionTumor Cells, Cultured
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 B7