2022
Carbonyl Posttranslational Modification Associated With Early-Onset Type 1 Diabetes Autoimmunity.
Yang ML, Connolly SE, Gee RJ, Lam TT, Kanyo J, Peng J, Guyer P, Syed F, Tse HM, Clarke SG, Clarke CF, James EA, Speake C, Evans-Molina C, Arvan P, Herold KC, Wen L, Mamula MJ. Carbonyl Posttranslational Modification Associated With Early-Onset Type 1 Diabetes Autoimmunity. Diabetes 2022, 71: 1979-1993. PMID: 35730902, PMCID: PMC9450849, DOI: 10.2337/db21-0989.Peer-Reviewed Original ResearchConceptsType 1 diabetesNOD miceMurine type 1 diabetesHuman type 1 diabetesDecreased glucose-stimulated insulin secretionAnti-insulin autoimmunityPrediabetic NOD miceGlucose-stimulated insulin secretionOnset Type 1T cell responsesOnset of hyperglycemiaCirculation of patientsAutoreactive CD4Insulin ratioInsulin secretionDiabetesPancreatic isletsType 1Islet proteinsOxidative stressAutoimmunitySelect groupMiceCarbonyl modificationOnset
2020
Insulin-Reactive T Cells Convert Diabetogenic Insulin-Reactive VH125 B Cells Into Tolerogenic Cells by Reducing Germinal Center T:B Cell Interactions in NOD Mice
Pearson JA, Li Y, Majewska-Szczepanik M, Guo J, Zhang L, Liu Y, Wong FS, Wen L. Insulin-Reactive T Cells Convert Diabetogenic Insulin-Reactive VH125 B Cells Into Tolerogenic Cells by Reducing Germinal Center T:B Cell Interactions in NOD Mice. Frontiers In Immunology 2020, 11: 585886. PMID: 33262765, PMCID: PMC7688534, DOI: 10.3389/fimmu.2020.585886.Peer-Reviewed Original ResearchConceptsB cell interactionsTransgenic NOD miceNOD miceT cellsB cellsT1D developmentAntigen-specific regulatory T cellsInsulin-reactive B cellsInsulin-reactive T cellsNon-obese diabetic (NOD) miceGerminal center TInsulin-reactive CD4Non-germinal centerCell interactionsCostimulatory molecule expressionRegulatory T cellsType 1 diabetesGC B cellsTolerogenic cellsAdoptive transferDiabetic miceTGFβ secretionMolecule expressionIgG isotypeKey autoantigen
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
2010
Immunotargeting of insulin reactive CD8 T cells to prevent Diabetes
Scott G, Fishman S, Siew L, Margalit A, Chapman S, Chervonsky A, Wen L, Gross G, Wong F. Immunotargeting of insulin reactive CD8 T cells to prevent Diabetes. Journal Of Autoimmunity 2010, 35: 390-397. PMID: 20850948, DOI: 10.1016/j.jaut.2010.08.005.Peer-Reviewed Original ResearchConceptsCD8 T cellsT cellsNOD miceAdoptive transferInsulin-reactive T cellsReactive CD8 T cellsInsulin-producing beta cellsPancreatic lymph nodesYoung NOD miceOnset of diabetesTransgenic T cellsCourse of diseaseType 1 diabetesFas-Fas ligand pathwayRelease of perforinSpontaneous diabetesAutoreactive CD4Lymph nodesImmune destructionLower incidenceBeta cellsDiabetesLigand pathwayPancreatic isletsTarget cells
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 ResearchIFN‐α Can Both Protect against and Promote the Development of Type 1 Diabetes
Wong F, Wen L. IFN‐α Can Both Protect against and Promote the Development of Type 1 Diabetes. Annals Of The New York Academy Of Sciences 2008, 1150: 187-189. PMID: 19120292, DOI: 10.1196/annals.1447.031.Peer-Reviewed Original Research
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
2006
TGF-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
2002
Analysis of structure and function relationships of an autoantigenic peptide of insulin bound to H-2Kd that stimulates CD8 T cells in insulin-dependent diabetes mellitus
Wong F, Moustakas A, Wen L, Papadopoulos G, Janeway C. Analysis of structure and function relationships of an autoantigenic peptide of insulin bound to H-2Kd that stimulates CD8 T cells in insulin-dependent diabetes mellitus. Proceedings Of The National Academy Of Sciences Of The United States Of America 2002, 99: 5551-5556. PMID: 11943852, PMCID: PMC122807, DOI: 10.1073/pnas.072037299.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutoantigensCD8-Positive T-LymphocytesCell DivisionCell LineChromium RadioisotopesDiabetes Mellitus, Type 1Dose-Response Relationship, DrugH-2 AntigensInsulinInterferon-gammaMiceMice, Inbred NODModels, MolecularPeptidesProtein BindingReceptor, InsulinStructure-Activity RelationshipTime FactorsConceptsT cellsCD8 T cell clonesInsulin-dependent diabetes mellitusInduction of CD8CD8 T cellsPathogenic T cellsT cell clonesT cell stimulationSmall glycine residueMHC-peptide complexesDiabetes mellitusAutoantigenic peptidesH-2KdCell clonesGlutamate residuesHydrophobic residuesGlycine residueReceptor interaction sitesCell stimulationFunctional assaysInteraction sitesFunction relationshipsPeptide substitutionProductive interactionHeavy chainInduction 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
Report From the 1st International NOD Mouse T-Cell Workshop and the Follow-Up Mini-Workshop
Kaufman D, Tisch R, Sarvetnick N, Chatenoud L, Harrison L, Haskins K, Quinn A, Sercarz E, Singh B, von Herrath M, Wegmann D, Wen L, Zekzer D. Report From the 1st International NOD Mouse T-Cell Workshop and the Follow-Up Mini-Workshop. Diabetes 2001, 50: 2459-2463. PMID: 11679422, DOI: 10.2337/diabetes.50.11.2459.Peer-Reviewed Original ResearchThe 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
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 Role of Lymphocyte Subsets in Accelerated Diabetes in Nonobese Diabetic–Rat Insulin Promoter–B7-1 (NOD-RIP-B7-1) Mice
Wong F, Visintin I, Wen L, Granata J, Flavell R, Janeway C. The Role of Lymphocyte Subsets in Accelerated Diabetes in Nonobese Diabetic–Rat Insulin Promoter–B7-1 (NOD-RIP-B7-1) Mice. Journal Of Experimental Medicine 1998, 187: 1985-1993. PMID: 9625758, PMCID: PMC2212360, DOI: 10.1084/jem.187.12.1985.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAge of OnsetAnimalsAntigen PresentationB7-1 AntigenCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesDiabetes Mellitus, Type 1Histocompatibility Antigens Class IIncidenceInsulinIslets of LangerhansLymphocyte SubsetsMiceMice, Inbred NODMice, TransgenicPromoter Regions, GeneticSpleenConceptsCD8 T cellsT cellsNOD miceB cellsAccelerated diabetesDiabetic miceB7-1 transgenic micePeripheral CD8 T cellsEffective antigen-presenting cellsMajor histocompatibility complex class IInsulin promoterCD4-/- miceMuMT-/- miceNontransgenic NOD miceNormal NOD miceNonobese diabetic (NOD) miceCD4 T cellsHistocompatibility complex class IAntigen-presenting cellsProvision of costimulationComplex class IPancreatic beta cellsWk of ageB220-positive B cellsIslet infiltrates
1997
Inhibition of Diabetes by an Insulin-Reactive CD4 T-Cell Clone in the Nonobese Diabetic Mouse
Zekzer D, Wong F, Wen L, Altieri M, Gurlo T, von Grafenstein H, Sherwin R. Inhibition of Diabetes by an Insulin-Reactive CD4 T-Cell Clone in the Nonobese Diabetic Mouse. Diabetes 1997, 46: 1124-1132. PMID: 9200646, DOI: 10.2337/diab.46.7.1124.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsCattleCD4 AntigensCell Adhesion MoleculesClone CellsCytokinesDiabetes Mellitus, Type 2Disease Models, AnimalDose-Response Relationship, DrugFemaleFlow CytometryInsulinMiceMice, Inbred NODPolymerase Chain ReactionRatsReceptors, Antigen, T-Cell, alpha-betaRNASpecific Pathogen-Free OrganismsTh1 CellsConceptsNOD miceDiabetic splenocytesIslet supernatantAdoptive transferDiabetic miceCD4 T-cell clonesInhibition of diabetesInjection of splenocytesPancreatic lymph nodesNonobese diabetic (NOD) miceAnti-transforming growthT cell clonesTh1 cell linesT cell receptorNOD isletsNOD splenocytesSpontaneous diabetesInsulin therapyLymph nodesAntibody treatmentTh1 cellsProtective effectDiabetesB chain peptideSplenocytes
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