2021
Toll-like receptor 7 deficiency suppresses type 1 diabetes development by modulating B-cell differentiation and function
Huang J, Peng J, Pearson JA, Efthimiou G, Hu Y, Tai N, Xing Y, Zhang L, Gu J, Jiang J, Zhao H, Zhou Z, Wong FS, Wen L. Toll-like receptor 7 deficiency suppresses type 1 diabetes development by modulating B-cell differentiation and function. Cellular & Molecular Immunology 2021, 18: 328-338. PMID: 33432061, PMCID: PMC8027372, DOI: 10.1038/s41423-020-00590-8.Peer-Reviewed Original ResearchConceptsType 1 diabetes developmentToll-like receptorsType 1 diabetesDiabetes developmentB cellsTLR7 deficiencyNOD miceB cell differentiationT cellsClassical MHC class I moleculesHuman type 1 diabetesImmunodeficient NOD miceNOD B cellsDiabetogenic T cellsAntigen-presenting functionNonobese diabetic (NOD) miceT cell responsesB cell functionMHC class I moleculesPattern recognition receptorsT cell activationPathogen molecular patternsClass I moleculesDiabetogenic CD4Cytotoxic CD8
2016
Epicutaneous immunization with ovalbumin and CpG induces TH1/TH17 cytokines, which regulate IgE and IgG2a production
Majewska-Szczepanik M, Askenase PW, Lobo FM, Marcińska K, Wen L, Szczepanik M. Epicutaneous immunization with ovalbumin and CpG induces TH1/TH17 cytokines, which regulate IgE and IgG2a production. Journal Of Allergy And Clinical Immunology 2016, 138: 262-273.e6. PMID: 26810716, PMCID: PMC5278675, DOI: 10.1016/j.jaci.2015.11.018.Peer-Reviewed Original ResearchConceptsSubcutaneous allergen-specific immunotherapyOVA-specific IgEEpicutaneous immunizationAllergen-specific immunotherapyAntigen-specific mannerT cell receptorAllergic diseasesToll-like receptor 9 agonistMyeloid differentiation primary response 88Differentiation primary response 88Course of allergyIL-17A dependentTolerability of immunotherapyLong-term remissionTH1/TH17 cytokinesReceptor 9 agonistAdoptive cell transferEosinophil peroxidase activityEpicutaneous treatmentRegulatory cellsTh17 cytokinesAtopic dermatitisIL-10IgG2a productionIgE synthesis
2014
IRAK-M Deficiency Promotes the Development of Type 1 Diabetes in NOD Mice
Tan Q, Majewska-Szczepanik M, Zhang X, Szczepanik M, Zhou Z, Wong FS, Wen L. IRAK-M Deficiency Promotes the Development of Type 1 Diabetes in NOD Mice. Diabetes 2014, 63: 2761-2775. PMID: 24696448, PMCID: PMC4113073, DOI: 10.2337/db13-1504.Peer-Reviewed Original ResearchConceptsDiabetogenic T cellsNOD miceRapid progressionT cellsInterleukin-1 receptor-associated kinase MOrgan-specific autoimmune diseasesType 1 diabetes mellitusAnti-insulin autoantibodiesImmunodeficient NOD miceImpaired glucose toleranceAntigen-presenting functionNonobese diabetic (NOD) miceToll-like receptor pathwayAntigen-presenting cellsEnhanced activationType 1 diabetesInnate immune pathwaysIRAK-M deficiencyInnate immune processesInsulin-secreting pancreatic β-cellsPancreatic β-cellsSevere insulitisAutoimmune diabetesDendritic cellsDiabetes mellitus
2011
Insulinoma-Released Exosomes or Microparticles Are Immunostimulatory and Can Activate Autoreactive T Cells Spontaneously Developed in Nonobese Diabetic Mice
Sheng H, Hassanali S, Nugent C, Wen L, Hamilton-Williams E, Dias P, Dai Y. Insulinoma-Released Exosomes or Microparticles Are Immunostimulatory and Can Activate Autoreactive T Cells Spontaneously Developed in Nonobese Diabetic Mice. The Journal Of Immunology 2011, 187: 1591-1600. PMID: 21734072, PMCID: PMC3150365, DOI: 10.4049/jimmunol.1100231.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigen-Presenting CellsCell Line, TumorCell-Derived MicroparticlesDiabetes Mellitus, ExperimentalDiabetes Mellitus, Type 1ExosomesFemaleHumansInsulinomaInsulin-Secreting CellsLymphocyte ActivationMaleMiceMice, Inbred NODMice, SCIDMyeloid Differentiation Factor 88Sex CharacteristicsTh1 CellsConceptsAutoreactive T cellsNOD miceAutoimmune targetT cellsCongenic miceNonobese diabetes-resistant miceHuman type 1 diabetesAg-specific immune responsesPrediabetic NOD micePancreatic lymph nodesNonobese diabetic (NOD) miceT cell responsesDiabetes-resistant miceAge-matched malesType 1 diabetesMyD88-dependent pathwayT cell proliferationResistant congenic miceInsulitis developmentPrediabetic NODInnate stimuliIslet destructionLymph nodesNOD femalesAutoimmune responseIL-10-conditioned dendritic cells prevent autoimmune diabetes in NOD and humanized HLA-DQ8/RIP-B7.1 mice
Tai N, Yasuda H, Xiang Y, Zhang L, Rodriguez-Pinto D, Yokono K, Sherwin R, Wong FS, Nagata M, Wen L. IL-10-conditioned dendritic cells prevent autoimmune diabetes in NOD and humanized HLA-DQ8/RIP-B7.1 mice. Clinical Immunology 2011, 139: 336-349. PMID: 21458378, DOI: 10.1016/j.clim.2011.03.003.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsB7-1 AntigenDendritic CellsDiabetes Mellitus, Type 1Disease Models, AnimalFemaleHLA-DQ AntigensHumansImmune ToleranceImmunophenotypingInsulin-Secreting CellsInterleukin-10Lymphocyte ActivationMaleMiceMice, Inbred BALB CMice, Inbred NODMice, SCIDMice, TransgenicSpecific Pathogen-Free OrganismsT-LymphocytesConceptsRIP-B7.1 miceAutoimmune diabetesIL-10IL-10-treated DCIL-12/23 p40T cell toleranceT cell proliferationDifferent animal modelsNew therapeutic interventionsSpontaneous diabetesRegulatory cellsDendritic cellsImmune toleranceCostimulatory moleculesIL-6IL-4T cellsAnimal modelsCell toleranceTherapeutic interventionsDiabetesCell proliferationT1D.MiceCells
2009
Activation of Insulin-Reactive CD8 T-Cells for Development of Autoimmune Diabetes
Wong FS, Siew LK, Scott G, Thomas IJ, Chapman S, Viret C, Wen L. Activation of Insulin-Reactive CD8 T-Cells for Development of Autoimmune Diabetes. Diabetes 2009, 58: 1156-1164. PMID: 19208910, PMCID: PMC2671054, DOI: 10.2337/db08-0800.Peer-Reviewed Original ResearchConceptsCD8 T cellsCD8 T cell clonesT cell clonesT cellsTransgenic miceT cell receptor transgenic miceAutoimmune CD8 T cellsInsulin-reactive T cellsCD8 single-positive thymocytesNonobese diabetic (NOD) miceReceptor transgenic miceDevelopment of autoimmuneTCR transgenic miceTransgenic T cellsThymic negative selectionSingle-positive thymocytesThymic insulin expressionDiabetogenic capacityIslet infiltratesSpontaneous diabetesPeripheral lymphClonotypic TCRDiabetic miceImmunodeficient NODNaïve phenotype
2008
Developing a Novel Model System to Target Insulin‐Reactive CD8 T Cells
Scott G, Fishman S, Margalit A, Siew L, Chapman S, Wen L, Gross G, Wong F. Developing a Novel Model System to Target Insulin‐Reactive CD8 T Cells. Annals Of The New York Academy Of Sciences 2008, 1150: 54-58. PMID: 19120267, DOI: 10.1196/annals.1447.040.Peer-Reviewed Original ResearchThe human T cell receptor Vβ repertoire of normal peripheral blood lymphocytes before and after mitogen stimulation
WONG F, HIBBERD M, WEN L, MILLWARD B, DEMAINF A. The human T cell receptor Vβ repertoire of normal peripheral blood lymphocytes before and after mitogen stimulation. Clinical & Experimental Immunology 2008, 92: 361-366. PMID: 8387412, PMCID: PMC1554814, DOI: 10.1111/j.1365-2249.1993.tb03405.x.Peer-Reviewed Original ResearchConceptsT cellsMitogen stimulationT cell antigen receptorPolymerase chain reactionT cell receptor Vβ repertoireFlow cytometryNormal peripheral blood lymphocytesMitogen-stimulated T cellsPeripheral blood lymphocytesTCR gene usagePeripheral T cellsT cell linesVβ repertoireUnstimulated T cellsBeta repertoireBlood lymphocytesHealthy individualsPCR methodBeta 6Cell antigen receptorGene usageAntigen receptorBeta 2Beta 5Chain reactionCD8+ T-cells and their interaction with other cells in damage to islet β-cells
Wong F, Siew L, Wen L. CD8+ T-cells and their interaction with other cells in damage to islet β-cells. Biochemical Society Transactions 2008, 36: 316-320. PMID: 18481949, DOI: 10.1042/bst0360316.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD8-Positive T-LymphocytesCell CommunicationHumansImmune SystemInsulin-Secreting CellsLymphocyte ActivationConceptsT cellsHuman type 1 diabetesAntigen-presenting cellsType 1 diabetesAutoimmune attackDiabetes developmentAntigenic targetsEffector stageToxic mediatorsVariety of cellsAnimal modelsTarget antigenImmune systemΒ-cellsMechanisms of damageCellsEarly stagesDamageCD8DiabetesCytokinesLymphocytesAntigen
2007
Functional inhibition related to structure of a highly potent insulin‐specific CD8 T cell clone using altered peptide ligands
de Marquesini L, Moustakas A, Thomas I, Wen L, Papadopoulos G, Wong F. Functional inhibition related to structure of a highly potent insulin‐specific CD8 T cell clone using altered peptide ligands. European Journal Of Immunology 2007, 38: 240-249. PMID: 18157812, PMCID: PMC2901522, DOI: 10.1002/eji.200737762.Peer-Reviewed Original ResearchConceptsCD8 T cellsT cellsCD8 T cell clonesAntagonist activityT cell functionT cell clonesProduction assaysMHC-peptide complexesTCR contact sitesNOD miceCD8 epitopesAgonist responsesTherapeutic useFunctional inhibitionCell clonesTCR stimulationCell functionPeptide ligandsNative peptideCellsPeptidesCytotoxicityAPLAssaysCD4
2001
Type 1 Diabetes-Predisposing MHC Alleles Influence the Selection of Glutamic Acid Decarboxylase (GAD) 65-Specific T Cells in a Transgenic Model
Abraham R, Wen L, Marietta E, David C. Type 1 Diabetes-Predisposing MHC Alleles Influence the Selection of Glutamic Acid Decarboxylase (GAD) 65-Specific T Cells in a Transgenic Model. The Journal Of Immunology 2001, 166: 1370-1379. PMID: 11145722, DOI: 10.4049/jimmunol.166.2.1370.Peer-Reviewed Original ResearchMeSH KeywordsAllelesAmino Acid SequenceAnimalsAntibody SpecificityCells, CulturedCytokinesDiabetes Mellitus, Type 1Disease Models, AnimalEpitopes, T-LymphocyteGenes, MHC Class IIGenetic Predisposition to DiseaseGlutamate DecarboxylaseHLA-DQ AntigensHLA-DR3 AntigenHumansImmunophenotypingIslets of LangerhansIsoenzymesLymphocyte ActivationMiceMice, Inbred C57BLMice, TransgenicMolecular Sequence DataRatsT-Lymphocyte SubsetsConceptsGlutamic acid decarboxylaseGAD 65T cellsDQ8 miceMixed Th1/Th2 cytokine profileEndogenous MHC class IISpontaneous T-cell reactivityTh1/Th2 cytokine profileGlutamic acid decarboxylase 65Self-reactive responsesT cell reactivityTh2 cytokine profileAutoantigen glutamic acid decarboxylase 65Type 1 diabetesMHC class IIDiabetes-associated genesCytokine profileIslet autoantigensHLA-DR3Immune toleranceHLA-DQ6Cell reactivitySelf-AgImmune responseHLA alleles
1999
Identification of an MHC class I-restricted autoantigen in type 1 diabetes by screening an organ-specific cDNA library
Wong F, Karttunen J, Dumont C, Wen L, Visintin I, Pilip I, Shastri N, Pamer E, Janeway C. Identification of an MHC class I-restricted autoantigen in type 1 diabetes by screening an organ-specific cDNA library. Nature Medicine 1999, 5: 1026-1031. PMID: 10470079, DOI: 10.1038/12465.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAutoantigensCD8-Positive T-LymphocytesClone CellsCloning, MolecularCOS CellsDiabetes Mellitus, Type 1Epitopes, T-LymphocyteGene LibraryHistocompatibility Antigens Class IInsulinInterferon-gammaIslets of LangerhansLymphocyte ActivationLymphocyte CountMiceMice, Inbred NODMice, Inbred StrainsOrgan SpecificityPeptidesConceptsType 1 diabetesAutoimmune diseasesT cellsPathogenic CD4 T cellsPathogenic CD8 T cellsNon-obese diabetic (NOD) miceCD8 T cell epitopesInsulin-producing pancreatic β-cellsAntigen-specific immunotherapyCD8 T lymphocytesCD8 T cellsCD4 T cellsT cell epitopesGood animal modelMHC class IIdentification of autoantigensPancreatic β-cellsDiabetic micePreventative therapyHuman diabetesT lymphocytesAnimal modelsImmune processesDiabetesΒ-cells
1998
The expression in vivo of a second isoform of pT alpha: implications for the mechanism of pT alpha action.
Barber D, Passoni L, Wen L, Geng L, Hayday A. The expression in vivo of a second isoform of pT alpha: implications for the mechanism of pT alpha action. The Journal Of Immunology 1998, 161: 11-6. PMID: 9647201, DOI: 10.4049/jimmunol.161.1.11.Peer-Reviewed Original Research
1996
CD8 T cell clones from young nonobese diabetic (NOD) islets can transfer rapid onset of diabetes in NOD mice in the absence of CD4 cells.
Wong FS, Visintin I, Wen L, Flavell RA, Janeway CA. CD8 T cell clones from young nonobese diabetic (NOD) islets can transfer rapid onset of diabetes in NOD mice in the absence of CD4 cells. Journal Of Experimental Medicine 1996, 183: 67-76. PMID: 8551245, PMCID: PMC2192404, DOI: 10.1084/jem.183.1.67.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsB7-1 AntigenBase SequenceCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesClone CellsCytokinesDiabetes Mellitus, Type 2FemaleImmunohistochemistryImmunotherapy, AdoptiveInsulinIslets of LangerhansLymphocyte ActivationMembrane GlycoproteinsMiceMice, Inbred BALB CMice, Inbred C57BLMice, Inbred NODMice, SCIDMolecular Sequence DataPancreasPerforinPore Forming Cytotoxic ProteinsPromoter Regions, GeneticConceptsT cell linesNOD miceT cellsCD8 T cell linesCD8 T cell clonesNonobese diabetic (NOD) miceCB17 SCID miceCD4 T cellsPathogenesis of diabetesT cell clonesCell linesIslets of LangerhansT cell antigen receptorNOD isletsCD4 cellsLymphocytic infiltrateNOD-SCIDDiabetic miceDiabetic isletsFemale NODRapid onsetCell antigen receptorH-2KdAntigen receptorMice
1994
Lymphocyte proliferation in mice congenitally deficient in T-cell receptor alpha beta + cells.
Viney J, Dianda L, Roberts S, Wen L, Mallick C, Hayday A, Owen M. Lymphocyte proliferation in mice congenitally deficient in T-cell receptor alpha beta + cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 1994, 91: 11948-11952. PMID: 7991563, PMCID: PMC45353, DOI: 10.1073/pnas.91.25.11948.Peer-Reviewed Original ResearchConceptsTCR gamma deltaTCR alpha betaGamma deltaAlpha betaT-cell receptor alpha betaT cell receptor expressionSurface activation markersAlpha mutant miceWild-type animalsActivation markersEnvironmental antigensLymphoid componentLymphocyte proliferationLymphoid organsLymphoid tissueReceptor expressionT cellsImmune responseMutant miceAbsolute numberMiceSubstantial proportionCell populationsPrimary regulatorBetaT Cell Clones Generated from Patients with Type 1 Diabetes Using Interleukin-2 Proliferate to Human Islet Antigens
Peakman M, Wen L, McNab G, Watkins P, Tan K, Vergani D. T Cell Clones Generated from Patients with Type 1 Diabetes Using Interleukin-2 Proliferate to Human Islet Antigens. Autoimmunity 1994, 17: 31-39. PMID: 8025212, DOI: 10.3109/08916939409014656.Peer-Reviewed Original ResearchMeSH KeywordsAdultAutoantigensAutoimmune DiseasesCD4 AntigensCD8 AntigensChildChild, PreschoolClone CellsDiabetes Mellitus, Type 1FemaleHumansInterleukin-2Islets of LangerhansLymphocyte ActivationMaleReceptors, Antigen, T-Cell, alpha-betaReceptors, Antigen, T-Cell, gamma-deltaReceptors, Interleukin-2T-Lymphocyte SubsetsConceptsT cell clonesT lymphocytesIslet antigensControl subjectsAntigen specificityType 1Cell clonesT cell populationsPeripheral blood lymphocytesIL-2 receptorActivated T lymphocytesDose-dependent fashionPrediabetic periodLiver membrane preparationsPeripheral bloodAutologous APCIL-2Blood lymphocytesPatientsHuman isletsLymphocytesMembrane preparationsProliferation assaysPathogenesisAntigen
1991
Transient T and B cell activation after neonatal induction of tolerance to MHC class II or Mls alloantigens.
Schurmans S, Brighouse G, Kramer G, Wen L, Izui S, Merino J, Lambert P. Transient T and B cell activation after neonatal induction of tolerance to MHC class II or Mls alloantigens. The Journal Of Immunology 1991, 146: 2152-60. PMID: 1672344, DOI: 10.4049/jimmunol.146.7.2152.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornAntibodies, AntinuclearAntigen-Antibody ComplexAntigens, Differentiation, T-LymphocyteAntigens, SurfaceAutoimmune DiseasesB-LymphocytesCD4-Positive T-LymphocytesCD8 AntigensHistocompatibility Antigens Class IHistocompatibility Antigens Class IIHypergammaglobulinemiaImmune ToleranceInterferon-gammaInterleukin-4Lymphocyte ActivationMajor Histocompatibility ComplexMiceMice, Inbred StrainsMinor Lymphocyte Stimulatory AntigensPlatelet CountReceptors, Antigen, T-CellThymus GlandT-LymphocytesConceptsMHC class IIB cell activationCell activationSpleen cellsClass IIAlloreactive CD4Neonatal injectionInjected miceT cellsF1 cellsTransient B cell activationIa AgLupus-like autoimmune syndromeSpecific toleranceClass IMajor histocompatibility complex class IFeatures of autoimmunityF1 spleen cellsTh cell responsesHistocompatibility complex class ICell-injected miceInduction of toleranceEarly postnatal periodComplex class IMHC class I
1988
Quantitative Analysis of Precursors Frequency of Rheumatoid Factor (RF) Producing Human B Cells
Vischer T, Werner-Favre C, Wen L, Zubler R. Quantitative Analysis of Precursors Frequency of Rheumatoid Factor (RF) Producing Human B Cells. Scandinavian Journal Of Rheumatology 1988, 17: 123-126. PMID: 3266359, DOI: 10.3109/03009748809096752.Peer-Reviewed Original Research
1987
Theoretical and Practical Aspects of B‐Cell Activation: Murine and Human Systems
Zubler R, Werner‐Favre C, Wen L, Sebcita K, Straub C. Theoretical and Practical Aspects of B‐Cell Activation: Murine and Human Systems. Immunological Reviews 1987, 99: 281-299. PMID: 2960608, DOI: 10.1111/j.1600-065x.1987.tb01181.x.Peer-Reviewed Original ResearchLimiting dilution assay for human B cells based on their activation by mutant EL4 thymoma cells: total and anti‐malaria responder B cell frequencies
Wen L, Hanvanich M, Werner‐Favre C, Brouwers N, Perrin L, Zubler R. Limiting dilution assay for human B cells based on their activation by mutant EL4 thymoma cells: total and anti‐malaria responder B cell frequencies. European Journal Of Immunology 1987, 17: 887-892. PMID: 3297736, DOI: 10.1002/eji.1830170624.Peer-Reviewed Original ResearchConceptsAntibody-secreting cellsB cellsPeripheral blood B cellsHuman B cell responsesB cell frequenciesB cell responsesBlood B cellsB cell activationHuman T cellsHuman B cellsMalaria infectionPeripheral bloodBlood donorsT cellsEL4 thymoma cellsMacrophage supernatantsControl groupCell frequencyCell activationCell responsesSpecificity repertoireInfectious diseasesClonal levelCulture systemMean amount