2008
Innate immunity and intestinal microbiota in the development of Type 1 diabetes
Wen L, Ley RE, Volchkov PY, Stranges PB, Avanesyan L, Stonebraker AC, Hu C, Wong FS, Szot GL, Bluestone JA, Gordon JI, Chervonsky AV. Innate immunity and intestinal microbiota in the development of Type 1 diabetes. Nature 2008, 455: 1109-1113. PMID: 18806780, PMCID: PMC2574766, DOI: 10.1038/nature07336.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBacteriaCD8-Positive T-LymphocytesDiabetes Mellitus, Type 1FemaleImmunity, InnateInterferon-gammaIntestinesIslets of LangerhansMaleMiceMice, Inbred NODMice, KnockoutMice, SCIDMolecular Sequence DataMyeloid Differentiation Factor 88PhylogenySpecific Pathogen-Free OrganismsTime FactorsConceptsType 1 diabetesNOD miceInnate immunityRapid innate immune responseDevelopment of diabetesNormal human gutInnate immune responseAdaptor protein MyD88Autoimmune diabetesTherapeutic optionsImmune responseNegative miceIntestinal microbiotaProtein MyD88DiabetesMiceGut microbesImmunityHuman gutMicrobial productsMyD88Influence predispositionIncidenceThe 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 reaction
2006
Modulatory Role of DR4- to DQ8-restricted CD4 T-Cell Responses and Type 1 Diabetes Susceptibility
Ge X, Piganelli J, Tse H, Bertera S, Mathews C, Trucco M, Wen L, Rudert W. Modulatory Role of DR4- to DQ8-restricted CD4 T-Cell Responses and Type 1 Diabetes Susceptibility. Diabetes 2006, 55: 3455-3462. PMID: 17130492, DOI: 10.2337/db06-0680.Peer-Reviewed Original ResearchConceptsT cell responsesHLA moleculesCaucasian type 1 diabetic patientsCD4 T cell activityCD4 T cell linesCD4 T cell responsesType 1 diabetic patientsHLA class II allelesCertain HLA moleculesT cell activityType 1 diabetesClass II allelesT cell linesSpecific DRB1HLA-DQ8Diabetic patientsModulatory roleDisease riskDQ8Type 1DR4Diabetes susceptibilityPeptide occupancyPrimary genetic determinantGenetic determinants
2004
What can the HLA transgenic mouse tell us about autoimmune diabetes?
Wong F, Wen L. What can the HLA transgenic mouse tell us about autoimmune diabetes? Diabetologia 2004, 47: 1476-1487. PMID: 15349728, DOI: 10.1007/s00125-004-1505-5.Peer-Reviewed Original ResearchConceptsHLA transgenic miceType 1 diabetes mellitusTransgenic miceDiabetes mellitusHLA class II allelesCD4 T lymphocytesAntigen-presenting moleculesClass II allelesPeptide-MHC complexesStudies of micePutative autoantigenParticular HLAT lymphocytesHLA moleculesPeptide antigensMHC complexesMiceDiseasePolygenic diseaseMellitusVivo roleInsultIntracellular processingImmunotherapyDiabetes
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
1998
Primary gamma delta cell clones can be defined phenotypically and functionally as Th1/Th2 cells and illustrate the association of CD4 with Th2 differentiation.
Wen L, Barber D, Pao W, Wong F, Owen M, Hayday A. Primary gamma delta cell clones can be defined phenotypically and functionally as Th1/Th2 cells and illustrate the association of CD4 with Th2 differentiation. The Journal Of Immunology 1998, 160: 1965-74. PMID: 9469460, DOI: 10.4049/jimmunol.160.4.1965.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsApoptosisB-LymphocytesCD4 AntigensCell DifferentiationCells, CulturedClone CellsCytokinesFas Ligand ProteinFas ReceptorGene ExpressionImmunoglobulin Class SwitchingImmunoglobulin IsotypesImmunophenotypingMembrane GlycoproteinsMiceMice, KnockoutMice, SCIDMolecular Sequence DataReceptors, Antigen, T-Cell, alpha-betaTh1 CellsTh2 CellsConceptsAlpha beta T cellsBeta T cellsGamma delta cellsT cellsCell clonesTh1/Th2 cellsGamma delta T cellsCD8 alpha betaDelta cellsDelta T cellsDivision of CD4Association of CD4Autoimmune diseasesCytokine expressionImmunoregulatory roleTh2 phenotypeTh2 subsetsTh2 cellsAntigen presentationCD4 expressionTh2 differentiationCD4Clonal levelAlpha betaStrong association
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