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
2007
Activated Insulin-Reactive CD8 T cells in NOD mice Cause Diabetes. (129.46)
Wong F, Siew L, Thomas I, Chapman S, Viret C, Wen L. Activated Insulin-Reactive CD8 T cells in NOD mice Cause Diabetes. (129.46). The Journal Of Immunology 2007, 178: s227-s227. DOI: 10.4049/jimmunol.178.supp.129.46.Peer-Reviewed Original ResearchCD8 T cellsTCR transgenic miceT cellsTransgenic miceNOD miceCD8 T cell clonesPredominance of CD8TCR transgenic cellsCD4 T cellsT cell clonesSingle-positive thymocytesT cell selectionSpontaneous diabetesAdoptive transferPeripheral lymphClonotypic TCRNaïve phenotypeCause diabetesDiabetesPositive thymocytesInsulin peptidesMiceCell clonesActivationCells
2006
Age-dependent loss of tolerance to an immunodominant epitope of glutamic acid decarboxylase in diabetic-prone RIP-B7/DR4 mice
Gebe J, Unrath K, Falk B, Ito K, Wen L, Daniels T, Lernmark Å, Nepom G. Age-dependent loss of tolerance to an immunodominant epitope of glutamic acid decarboxylase in diabetic-prone RIP-B7/DR4 mice. Clinical Immunology 2006, 121: 294-304. PMID: 16979383, PMCID: PMC1850983, DOI: 10.1016/j.clim.2006.08.002.Peer-Reviewed Original ResearchConceptsGlial fibrillary acidic proteinNon-diabetic miceGlutamic acid decarboxylaseImmunodominant epitopesAcid decarboxylaseIslet-specific glucose-6-phosphatase catalytic subunit-related proteinHLA transgenic miceMean onset ageFibrillary acidic proteinAge-dependent lossIslet infiltratesOvert diabetesDiabetic miceFemale miceHistological evidenceMale miceDR4 miceYoung miceOnset ageProliferative responseDiabetic diseaseTransgenic miceImmunogenic epitopesAcidic proteinMiceTGF-β signaling is required for the function of insulin-reactive T regulatory cells
Du W, Wong FS, Li MO, Peng J, Qi H, Flavell RA, Sherwin R, Wen L. TGF-β signaling is required for the function of insulin-reactive T regulatory cells. Journal Of Clinical Investigation 2006, 116: 1360-1370. PMID: 16670772, PMCID: PMC1451206, DOI: 10.1172/jci27030.Peer-Reviewed Original ResearchConceptsT cellsNOD miceRegulatory cellsDominant negative TGF-beta receptor type IITransgenic miceTCR transgenic T cellsTGF-beta receptor type IIDiabetic NOD miceDiabetogenic spleen cellsDiabetogenic T cellsTCR transgenic miceTransgenic T cellsReceptor type IIBDC2.5 miceAdoptive transferTGF-beta signalingSpleen cellsParacrine mannerGranule antigensAutocrine mannerSuppressive propertiesDiabetesMiceTarget cellsSpontaneous development
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
2003
Autoimmune diabetes in HLA‐DR3/DQ8 transgenic mice expressing the co‐stimulatory molecule B7‐1 in the β cells of islets of Langerhans
Rajagopalan G, Kudva YC, Chen L, Wen L, David CS. Autoimmune diabetes in HLA‐DR3/DQ8 transgenic mice expressing the co‐stimulatory molecule B7‐1 in the β cells of islets of Langerhans. International Immunology 2003, 15: 1035-1044. PMID: 12917255, DOI: 10.1093/intimm/dxg103.Peer-Reviewed Original ResearchConceptsCo-stimulatory molecules B7-1Incidence of diabetesTransgenic miceB7-1Autoimmune diabetesHLA-DQ8HLA-DR3T cellsBeta cellsBeta-cell toxin streptozotocinHLA class II associationsDQ8 transgenic micePresence of DR3HLA transgenic miceAntibody-mediated depletionPathogenesis of T1D.Class II associationsHLA class IIWhole-body irradiationPancreatic beta cellsNon-specific activationSpontaneous diabetesToxin streptozotocinDiabetogenic potentialSTZ treatmentThe study of HLA class II and autoimmune diabetes.
Wong F, Wen L. The study of HLA class II and autoimmune diabetes. 2003, 3: 1-15. PMID: 12558070, DOI: 10.2174/1566524033361591.Peer-Reviewed Original ResearchConceptsHLA moleculesTransgenic miceHuman leucocyte antigens DR3HLA transgenic miceCD4 T lymphocytesHLA class IIAntigen-specific cellsT cell epitopesMHC-peptide complexesPeptide-MHC complexesPutative autoantigenDiabetes mellitusAutoimmune diseasesAntigens DR3T lymphocytesCell epitopesClass IIPeptide antigensMajor histocompatibility complex class II lociMHC complexesDiseaseClass II lociDevelopment of reagentsMiceFurther studies
2002
Induction and acceleration of insulitis/diabetes in mice with a viral mimic (polyinosinic-polycytidylic acid) and an insulin self-peptide
Moriyama H, Wen L, Abiru N, Liu E, Yu L, Miao D, Gianani R, Wong F, Eisenbarth G. Induction and acceleration of insulitis/diabetes in mice with a viral mimic (polyinosinic-polycytidylic acid) and an insulin self-peptide. Proceedings Of The National Academy Of Sciences Of The United States Of America 2002, 99: 5539-5544. PMID: 11943868, PMCID: PMC122805, DOI: 10.1073/pnas.082120099.Peer-Reviewed Original ResearchConceptsT lymphocytesB7-1 transgenic miceBALB/c miceAnti-islet autoimmunityExperimental autoimmune diabetesAutoreactive T lymphocytesB7-1 moleculeCD4 T lymphocytesType 1 diabetesPolyinosinic-polycytidylic acidAutoimmune diabetesInsulin autoantibodiesC micePeptide immunizationSimultaneous administrationDisease inductionMurine modelMouse modelDiabetesTransgenic miceInsulin peptidesMiceImmunizationPolyICViral mimic
2001
The regulatory role of DR4 in a spontaneous diabetes DQ8 transgenic model
Wen L, Chen N, Tang J, Sherwin R, Wong F. The regulatory role of DR4 in a spontaneous diabetes DQ8 transgenic model. Journal Of Clinical Investigation 2001, 107: 871-880. PMID: 11285306, PMCID: PMC199575, DOI: 10.1172/jci11708.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone Marrow CellsCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell DifferentiationDiabetes Mellitus, Type 1Disease Models, AnimalFemaleGene ExpressionHistocompatibility Antigens Class IIHLA-DQ AntigensHLA-DR4 AntigenIncidenceInsulinMaleMiceMice, Inbred C57BLMice, TransgenicMicrosatellite RepeatsPancreasSialadenitisSpleenTh2 CellsTransgenesConceptsMHC class II moleculesSpontaneous diabetesClass II moleculesTransgenic miceT cellsHLA-DQ8Diabetogenic effectMouse MHC class II moleculesHLA-DR transgenic miceTh2-like immune responsesHuman type 1 diabetesAutoreactive T cellsDouble transgenic miceType 1 diabetesC57BL/6 transgenic miceTh2-like phenotypePancreatic beta cellsExpression of DR4DQ8 allelesDiabetes developmentCostimulatory moleculesHLA-DQImmune responseBeta cellsDiabetes
2000
In Vivo Evidence for the Contribution of Human Histocompatibility Leukocyte Antigen (Hla)-Dq Molecules to the Development of Diabetes
Wen L, Wong F, Tang J, Chen N, Altieri M, David C, Flavell R, Sherwin R. In Vivo Evidence for the Contribution of Human Histocompatibility Leukocyte Antigen (Hla)-Dq Molecules to the Development of Diabetes. Journal Of Experimental Medicine 2000, 191: 97-104. PMID: 10620608, PMCID: PMC2195792, DOI: 10.1084/jem.191.1.97.Peer-Reviewed Original ResearchConceptsClass II moleculesMHC class II moleculesGlutamic acid decarboxylaseRat insulin promoterSpontaneous diabetesB7-1T cellsBeta cellsMouse MHC class II moleculesTransgenic miceHuman histocompatibility leukocyte antigenHuman type 1 diabetesMajor histocompatibility complex (MHC) class II moleculesCostimulatory molecules B7-1Human MHC class II moleculesVivo evidenceHistocompatibility leukocyte antigenDevelopment of diabetesType 1 diabetesMHC class IIC57BL/6 transgenic miceMurine MHC class IIPancreatic beta cellsVivo experimental evidenceDiabetogenic role