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
Enhanced B7 Costimulatory Molecule Expression In Inflammatory Human Sural Nerve Biopsies
Kiefer R, Dangond F, Mueller M, Toyka K, Hafler D, Hartung H. Enhanced B7 Costimulatory Molecule Expression In Inflammatory Human Sural Nerve Biopsies. Journal Of The Peripheral Nervous System 2001, 6: 64-64. DOI: 10.1046/j.1529-8027.2001.01008-15.x.Peer-Reviewed Original ResearchChronic inflammatory demyelinating polyneuropathyGuillain-Barre syndromeSural nerve biopsyPeripheral nervous systemB7-1Nerve biopsyB7-2 mRNAPolymerase chain reactionB7-2Nervous systemCases of GBSCostimulatory molecules B7-1Th-2 phenotypeInflammatory demyelinating polyneuropathyB7-1 proteinCostimulatory molecule expressionT cell responsesEffective antigen presentationCases of neuroborreliosisHuman sural nerve biopsiesCIDP casesCIDP variantsDemyelinating polyneuropathyEndoneurial macrophagesDisease course
2000
Enhanced 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 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
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
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 CellsB-LymphocytesB7-1 AntigenCD40 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