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
Interleukin-10+ Regulatory B Cells Arise Within Antigen-Experienced CD40+ B Cells to Maintain Tolerance to Islet Autoantigens
Kleffel S, Vergani A, Tezza S, Nasr M, Niewczas MA, Wong S, Bassi R, D’Addio F, Schatton T, Abdi R, Atkinson M, Sayegh MH, Wen L, Wasserfall CH, O’Connor K, Fiorina P. Interleukin-10+ Regulatory B Cells Arise Within Antigen-Experienced CD40+ B Cells to Maintain Tolerance to Islet Autoantigens. Diabetes 2014, 64: 158-171. PMID: 25187361, PMCID: PMC4274804, DOI: 10.2337/db13-1639.Peer-Reviewed Original ResearchConceptsIslet autoantigensB cellsT1D patientsInterleukin-10IL-10-producing B cellsHyperglycemic nonobese diabetic miceRegulatory B-cell responsesAutoreactive T cell responsesT cell-mediated responsesRole of BregsB-cell depletionRegulatory B cellsNonobese diabetic (NOD) miceNOD mouse modelT cell responsesB cell responsesType 1 diabetesB cell receptorAdoptive transferDiabetic miceAutoimmune diseasesHuman ILHyperglycemic miceMouse modelBregs
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
Expression of Diabetes-Associated Genes by Dendritic Cells and CD4 T Cells Drives the Loss of Tolerance in Nonobese Diabetic Mice
Hamilton-Williams EE, Martinez X, Clark J, Howlett S, Hunter KM, Rainbow DB, Wen L, Shlomchik MJ, Katz JD, Beilhack GF, Wicker LS, Sherman LA. Expression of Diabetes-Associated Genes by Dendritic Cells and CD4 T Cells Drives the Loss of Tolerance in Nonobese Diabetic Mice. The Journal Of Immunology 2009, 183: 1533-1541. PMID: 19592648, PMCID: PMC2733871, DOI: 10.4049/jimmunol.0900428.Peer-Reviewed Original ResearchConceptsRegulatory T cellsT cellsDendritic cellsNOD miceProtective allelesCD4 T-cell expressionTolerance defectsImmune tolerance resultsPancreatic lymph nodesCD8 T cellsNonobese diabetic (NOD) miceCD4 T cellsT cell expressionLoss of toleranceIL-2 productionDiabetes 3Lymph nodesDiabetic miceIslet AgsNOD alleleCell expressionMiceSpontaneous developmentIdd3Tolerance results
2008
Differences in immune recognition of cytochrome P4502D6 by liver kidney microsomal (LKM) antibody in autoimmune hepatitis and chronic hepatitis C virus infection
MA Y, PEAKMAN M, LOBO-YEO A, WEN L, LENZI M, GÄKEN J, FARZANEH F, MIELI-VERGANI G, BIANCHI F, VERGANI D. Differences in immune recognition of cytochrome P4502D6 by liver kidney microsomal (LKM) antibody in autoimmune hepatitis and chronic hepatitis C virus infection. Clinical & Experimental Immunology 2008, 97: 94-99. PMID: 8033426, PMCID: PMC1534799, DOI: 10.1111/j.1365-2249.1994.tb06585.x.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAntibody SpecificityAutoantibodiesAutoantigensAutoimmune DiseasesB-LymphocytesChildChild, PreschoolCytochrome P-450 CYP2D6Cytochrome P-450 Enzyme SystemFemaleHepatitisHepatitis CHepatitis, ChronicHumansInfantMaleMiddle AgedMixed Function OxygenasesRecombinant Fusion ProteinsConceptsChronic hepatitis C virus (HCV) infectionHepatitis C virus infectionLKM-1 antibodiesAutoimmune hepatitisC virus infectionLKM-1HCV infectionVirus infectionCytochrome P4502D6Liver kidney microsomal antibodiesClassical autoimmune hepatitisKidney microsomal antibodyChronic HCV infectionLymphoblastoid B cell linesMicrosomal antibodiesPositive patientsLiver diseaseB cell linesHCVPatientsImmune recognitionMolecular mimicryRecombinant CYP2D6Western blotCYP2D6
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 chain
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 Research
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
1994
T 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