2004
An Autoimmune Disease-Associated CTLA-4 Splice Variant Lacking the B7 Binding Domain Signals Negatively in T Cells
Vijayakrishnan L, Slavik JM, Illés Z, Greenwald RJ, Rainbow D, Greve B, Peterson LB, Hafler DA, Freeman GJ, Sharpe AH, Wicker LS, Kuchroo VK. An Autoimmune Disease-Associated CTLA-4 Splice Variant Lacking the B7 Binding Domain Signals Negatively in T Cells. Immunity 2004, 20: 563-575. PMID: 15142525, DOI: 10.1016/s1074-7613(04)00110-4.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntigens, CDAntigens, DifferentiationAutoimmune DiseasesB7-1 AntigenBlotting, WesternCloning, MolecularCTLA-4 AntigenFemaleFlow CytometryHumansMembrane ProteinsMiceMice, Inbred NODMolecular Sequence DataReceptors, Antigen, T-CellReverse Transcriptase Polymerase Chain ReactionRNA, MessengerSignal TransductionT-LymphocytesConceptsCytotoxic T-lymphocyte-associated antigen 4T cell responsesT cellsNOD miceAutoimmune diseasesT cell-mediated autoimmune diseaseT-lymphocyte-associated antigen 4Cell responsesCell-mediated autoimmune diseaseSusceptible NOD miceRegulatory T cellsNOD congenic miceCTLA-4 locusAntigen-4B7-1B7-2Primary T cellsCongenic miceSplice variantsMiceNegative signalingMYPPPY motifDiseaseType IGenetic linkage
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
Immunological Memory: Contribution of Memory B Cells Expressing Costimulatory Molecules in the Resting State
Bar-Or A, Oliveira E, Anderson D, Krieger J, Duddy M, O’Connor K, Hafler D. Immunological Memory: Contribution of Memory B Cells Expressing Costimulatory Molecules in the Resting State. The Journal Of Immunology 2001, 167: 5669-5677. PMID: 11698439, DOI: 10.4049/jimmunol.167.10.5669.Peer-Reviewed Original ResearchConceptsMemory B cellsB cell subsetsB cellsCell subsetsCostimulatory moleculesB cell memory compartmentMemory responsesImmune memory responseDistinct B cell subsetsHuman memory B cellsHumoral memory responsesHuman B cellsTh cellsImmunological memoryT cellsMemory compartmentPoor APCsMurine systemNovel subpopulationRelative paucityCellsCD4+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
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 responseEnhanced B7 costimulatory molecule expression in inflammatory human sural nerve biopsies
Kiefer R, Dangond F, Mueller M, Toyka KV, Hafler DA, Hartung HP. Enhanced B7 costimulatory molecule expression in inflammatory human sural nerve biopsies. Journal Of Neurology Neurosurgery & Psychiatry 2000, 69: 362. PMID: 10945811, PMCID: PMC1737105, DOI: 10.1136/jnnp.69.3.362.Peer-Reviewed Original ResearchConceptsChronic inflammatory demyelinating polyneuropathyGuillain-Barré syndromeSural nerve biopsyPeripheral nervous systemB7-1Nerve biopsyB7-2 mRNAB7 moleculesPolymerase chain reactionB7-2Nervous systemCases of GBSNon-inflammatory control groupCostimulatory molecules B7-1B7-1 mRNANon-inflammatory controlsTh-2 phenotypeInflammatory demyelinating polyneuropathyB7-1 proteinCostimulatory molecule expressionT cell responsesEffective antigen presentationCases of neuroborreliosisHuman sural nerve biopsiesCIDP casesA 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 subjectsPatients
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 yearPathwayAutoimmunityCD28InitiationCostimulationMolecular pathogenesis of multiple sclerosis
Bar-Or A, Oliveira E, Anderson D, Hafler D. Molecular pathogenesis of multiple sclerosis. Journal Of Neuroimmunology 1999, 100: 252-259. PMID: 10695735, DOI: 10.1016/s0165-5728(99)00193-9.Peer-Reviewed Original ResearchConceptsMultiple sclerosisT cellsMyelin-reactive T cellsCentral nervous system white matterB7 costimulatory pathwayNervous system white matterDifferential activation statesMacrophage infiltratesMS patientsAxonal injuryNeurological functionProinflammatory cellsProinflammatory cytokinesCostimulatory pathwayInflammatory diseasesMS lesionsMolecular pathogenesisWhite matterMolecular mimicryMatrix metalloproteinasesNormal individualsAdhesion moleculesSelective expressionSclerosisActivation stateDirect analysis of viral-specific CD8+ T cells with soluble HLA-A2/Tax11-19 tetramer complexes in patients with human T cell lymphotropic virus-associated myelopathy.
Bieganowska K, Höllsberg P, Buckle G, Lim D, Greten T, Schneck J, Altman J, Jacobson S, Ledis S, Hanchard B, Chin J, Morgan O, Roth P, Hafler D. Direct analysis of viral-specific CD8+ T cells with soluble HLA-A2/Tax11-19 tetramer complexes in patients with human T cell lymphotropic virus-associated myelopathy. The Journal Of Immunology 1999, 162: 1765-71. PMID: 9973440, DOI: 10.4049/jimmunol.162.3.1765.Peer-Reviewed Original ResearchMeSH KeywordsAdultB7-1 AntigenCD28 AntigensCD8-Positive T-LymphocytesFemaleGene Products, taxHLA-A2 AntigenHuman T-lymphotropic virus 1HumansLymphocyte ActivationMaleMiddle AgedParaparesis, Tropical SpasticPeptide FragmentsPhenotypeProtein ConformationReceptors, Antigen, T-Cell, alpha-betaReceptors, ChemokineReceptors, Interleukin-2SolubilityConceptsT cellsIL-2RMHC class I tetramersHuman T-cell lymphotropic virusViral-specific CD8Class I tetramersProgressive neurologic diseaseDifferent chemokine receptorsHLA-A2 alleleCentral nervous systemTCR Vbeta chainsReactive CD8TCR usageInflammatory infiltrateVbeta chainsChemokine receptorsNeurologic diseaseImmune responseCD8Lymphotropic virusMyelopathyNervous systemPatientsHTLVClonal expansion
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
Weak peptide agonists reveal functional differences in B7-1 and B7-2 costimulation of human T cell clones.
Anderson DE, Ausubel LJ, Krieger J, Höllsberg P, Freeman GJ, Hafler DA. Weak peptide agonists reveal functional differences in B7-1 and B7-2 costimulation of human T cell clones. The Journal Of Immunology 1997, 159: 1669-75. PMID: 9257827, DOI: 10.4049/jimmunol.159.4.1669.Peer-Reviewed Original ResearchConstitutive expression of costimulatory molecules by human microglia and its relevance to CNS autoimmunity
Dangond F, Windhagen A, Groves C, Hafler D. Constitutive expression of costimulatory molecules by human microglia and its relevance to CNS autoimmunity. Journal Of Neuroimmunology 1997, 76: 132-138. PMID: 9184642, DOI: 10.1016/s0165-5728(97)00043-x.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAutoimmunityB7-1 AntigenBrainCells, CulturedChild, PreschoolFemaleHumansMaleMicrogliaConceptsCentral nervous systemCostimulatory moleculesHuman microgliaMyelin-reactive T cellsTh1 T cell responsesExpression of B7.1Reactive T cellsT cell responsesMultiple sclerosis plaquesT cell surface moleculesB7.2 costimulatory moleculesMHC-antigen complexesT cell activationT cell receptorCNS autoimmunityCNS inflammationB7.2 expressionBiopsy specimensB7 familyT cellsNormal brainMicrogliaNervous systemB7.1High expression
1996
Induction of anergy in CD8 T cells by B cell presentation of antigen.
Höllsberg P, Batra V, Dressel A, Hafler DA. Induction of anergy in CD8 T cells by B cell presentation of antigen. The Journal Of Immunology 1996, 157: 5269-76. PMID: 8955172, DOI: 10.4049/jimmunol.157.12.5269.Peer-Reviewed Original ResearchMeSH KeywordsAntigen-Presenting CellsB7-1 AntigenB-LymphocytesCD40 LigandCD8-Positive T-LymphocytesCell LineClonal AnergyCytotoxicity, ImmunologicGene ExpressionHumansImmunologic MemoryInterleukin-2Lymphocyte ActivationMembrane GlycoproteinsReceptors, Antigen, T-CellSignal TransductionTranscription, GeneticConceptsCD8 T cellsT cell clonesInduction of anergyT cellsB cellsMononuclear cellsB7-1Cell clonesAg stimulationAnergic CD8 T cellsPeptide-pulsed B cellsPeptide-pulsed target cellsCD4 T-cell clonesCD8 T cell clonesSecondary Ag challengeExogenous IL-2B7-2 costimulationB cell presentationT cell anergyIL-2 secretionNormal proliferative responseIL-2 mRNA transcriptionT cell stimulationEarly tyrosine phosphorylationAdequate costimulationActivation of human T cell lymphotropic virus type I-infected T cells is independent of B7 costimulation.
Scholz C, Freeman GJ, Greenfield EA, Hafler DA, Höllsberg P. Activation of human T cell lymphotropic virus type I-infected T cells is independent of B7 costimulation. The Journal Of Immunology 1996, 157: 2932-8. PMID: 8816399, DOI: 10.4049/jimmunol.157.7.2932.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalAntigen-Presenting CellsAntigens, CDAutoimmunityB7-1 AntigenB7-2 AntigenBase SequenceCD28 AntigensCHO CellsClone CellsCricetinaeCricetulusEnzyme ActivationHLA-DR AntigensHLA-DRB1 ChainsHuman T-lymphotropic virus 1HumansInterferon-gammaInterleukin-4Interleukin-5Janus Kinase 3Lymphocyte ActivationMembrane GlycoproteinsMolecular Sequence DataMyelin Basic ProteinProtein-Tyrosine KinasesSignal TransductionT-Lymphocyte SubsetsTransfectionConceptsHuman T-cell lymphotropic virus type ILymphotropic virus type IB7 costimulationT cell clonesT cellsB7-1Virus type IIL-4IL-5B7-2IFN-gammaAutoreactive T cell responsesCell clonesAg-specific signalAutoimmune-like diseaseT cell responsesAutoreactive T cellsHTLV-I infectionB7-2 costimulationB7-2 moleculesUninfected T cellsType IAutoimmune responseB7 expressionCytokine secretion
1995
Expression of costimulatory molecules B7-1 (CD80), B7-2 (CD86), and interleukin 12 cytokine in multiple sclerosis lesions.
Windhagen A, Newcombe J, Dangond F, Strand C, Woodroofe MN, Cuzner ML, Hafler DA. Expression of costimulatory molecules B7-1 (CD80), B7-2 (CD86), and interleukin 12 cytokine in multiple sclerosis lesions. Journal Of Experimental Medicine 1995, 182: 1985-1996. PMID: 7500044, PMCID: PMC2192240, DOI: 10.1084/jem.182.6.1985.Peer-Reviewed Original ResearchConceptsAutoreactive T cellsMultiple sclerosisT cellsB7-1Autoimmune diseasesCostimulatory moleculesMS plaquesB7-2T cell-mediated autoimmune diseaseInitiation of MSMyelin-autoreactive T cellsCell-mediated autoimmune diseaseSelf-reactive T cellsCostimulatory molecules B7-1Acute MS plaquesAutoimmune animal modelsInterleukin-12 cytokinesPutative autoimmune diseaseSemiquantitative reverse transcriptase-polymerase chain reactionReverse transcriptase-polymerase chain reactionExpression of cytokinesTranscriptase-polymerase chain reactionT cell activationMultiple sclerosis lesionsInflammatory cuffs
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