2017
Podoplanin is a negative regulator of Th17 inflammation
Nylander AN, Ponath GD, Axisa PP, Mubarak M, Tomayko M, Kuchroo VK, Pitt D, Hafler DA. Podoplanin is a negative regulator of Th17 inflammation. JCI Insight 2017, 2: e92321. PMID: 28878118, PMCID: PMC5621890, DOI: 10.1172/jci.insight.92321.Peer-Reviewed Original ResearchConceptsT cellsIL-17IL-17 secretionDistinct cytokine profilesInflammatory gene signatureTh17-polarizing conditionsTh17 cellsCytokine profileCell subsetsInflammatory responseSkin biopsiesMouse modelPDPN expressionMultiple organsSkin diseasesGene signatureInflammationLymphatic systemCLEC-2PDPNRecent dataDifferent subpopulationsCellsTranscriptional profilesShRNA gene
2007
The role of the Toll receptor pathway in susceptibility to inflammatory bowel diseases
De Jager PL, Franchimont D, Waliszewska A, Bitton A, Cohen A, Langelier D, Belaiche J, Vermeire S, Farwell L, Goris A, Libioulle C, Jani N, Dassopoulos T, Bromfield GP, Dubois B, Cho JH, Brant SR, Duerr RH, Yang H, Rotter JI, Silverberg MS, Steinhart AH, Daly MJ, Podolsky DK, Louis E, Hafler DA, Rioux JD. The role of the Toll receptor pathway in susceptibility to inflammatory bowel diseases. Genes & Immunity 2007, 8: 387-397. PMID: 17538633, DOI: 10.1038/sj.gene.6364398.Peer-Reviewed Original ResearchConceptsInflammatory bowel diseaseCases of IBDRisk of IBDToll-like receptorsBowel diseaseIBD risk allelesUlcerative colitisCrohn's diseaseTLR4 pathwayIBD pathophysiologyIntestinal floraTLR pathwayTLR4 allelesHost defenseReceptor pathwayRisk allelesTLR genesDiseaseTLR4Modest effectHost/pathogen interactionsTIRAPAssociationReplication studyRisk
2004
T Cell Ig- and Mucin-Domain-Containing Molecule-3 (TIM-3) and TIM-1 Molecules Are Differentially Expressed on Human Th1 and Th2 Cells and in Cerebrospinal Fluid-Derived Mononuclear Cells in Multiple Sclerosis
Khademi M, Illés Z, Gielen AW, Marta M, Takazawa N, Baecher-Allan C, Brundin L, Hannerz J, Martin C, Harris RA, Hafler DA, Kuchroo VK, Olsson T, Piehl F, Wallström E. T Cell Ig- and Mucin-Domain-Containing Molecule-3 (TIM-3) and TIM-1 Molecules Are Differentially Expressed on Human Th1 and Th2 Cells and in Cerebrospinal Fluid-Derived Mononuclear Cells in Multiple Sclerosis. The Journal Of Immunology 2004, 172: 7169-7176. PMID: 15153541, DOI: 10.4049/jimmunol.172.11.7169.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedCell LineCell PolarityCerebrospinal FluidCytokinesFemaleGene Expression RegulationHepatitis A Virus Cellular Receptor 1Hepatitis A Virus Cellular Receptor 2HumansMaleMembrane GlycoproteinsMembrane ProteinsMiddle AgedMultiple SclerosisReceptors, VirusRNA, MessengerTh1 CellsTh2 CellsConceptsCerebrospinal fluid mononuclear cellsFluid mononuclear cellsT cell IgMononuclear cellsTim-3Multiple sclerosisTh2 cellsTIM-1Human Th1TIM moleculesMucin-domain-containing moleculesTim-3 mRNA levelsTh2-mediated diseasesHigh expressionExperimental autoimmune encephalomyelitisHuman autoimmune diseasesTIM-1 expressionIFN-gamma mRNAReal-time RT-PCRTim-1 polymorphismsTh1 cell clonesHigher mRNA expressionAirway hyperreactivityClinical remissionAutoimmune encephalomyelitis
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
A 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
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 expressionWeak 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 ResearchB7.2 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 BindingT-LymphocytesThymomaThymus NeoplasmsTransfectionTumor Cells, CulturedIncreased interleukin 12 production in progressive multiple sclerosis: Induction by activated CD4+ T cells via CD40 ligand
Balashov K, Smith D, Khoury S, Hafler D, Weiner H. Increased interleukin 12 production in progressive multiple sclerosis: Induction by activated CD4+ T cells via CD40 ligand. Proceedings Of The National Academy Of Sciences Of The United States Of America 1997, 94: 599-603. PMID: 9012830, PMCID: PMC19559, DOI: 10.1073/pnas.94.2.599.Peer-Reviewed Original ResearchConceptsIL-12 secretionIFN-gamma secretionMS patientsMultiple sclerosisT cellsIL-12Anti-CD40 ligand antibodyTh1-type immune activationCell-mediated autoimmune diseaseProgressive MS patientsProgressive multiple sclerosisIFN-gamma administrationRelapsing-remitting patientsExacerbation of diseaseInterleukin-12 productionChronic inflammatory diseaseCD40 ligand expressionCentral nervous systemActivated T cellsImmune interventionImmune activationAutoimmune diseasesInterleukin-12Inflammatory diseasesCD40 ligand
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
1991
Presentation of autoantigen by human T cells.
LaSalle JM, Ota K, Hafler DA. Presentation of autoantigen by human T cells. The Journal Of Immunology 1991, 147: 774-80. PMID: 1713605, DOI: 10.4049/jimmunol.147.3.774.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAntigens, CDAntigens, Differentiation, T-LymphocyteAntigens, SurfaceAutoantigensCD2 AntigensCD58 AntigensEpitopesHistocompatibility AntigensHLA-D AntigensHumansIntegrin beta1Leukocyte Common AntigensLymphocyte ActivationLymphocyte Function-Associated Antigen-1Membrane GlycoproteinsMolecular Sequence DataMyelin Basic ProteinReceptors, ImmunologicT-LymphocytesConceptsT cell clonesMBP-reactive T cell clonesAutologous T cellsMyelin basic proteinMHC class IIT cellsHuman T cellsCell clonesAdhesion molecules LFA-3Class IIReactive T cell clonesWhole myelin basic proteinPresentation of autoantigensT cell interactionsActivated T cellsT cell presentationTCR-mediated responsesAg preparationsImmune responseMHC classSelf-AgForeign AgsInflammatory sitesCell presentationLFA-3
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