2015
Maternal Antibiotic Treatment Protects Offspring from Diabetes Development in Nonobese Diabetic Mice by Generation of Tolerogenic APCs
Hu Y, Peng J, Tai N, Hu C, Zhang X, Wong FS, Wen L. Maternal Antibiotic Treatment Protects Offspring from Diabetes Development in Nonobese Diabetic Mice by Generation of Tolerogenic APCs. The Journal Of Immunology 2015, 195: 4176-4184. PMID: 26401004, PMCID: PMC4765177, DOI: 10.4049/jimmunol.1500884.Peer-Reviewed Original ResearchConceptsNOD miceTolerogenic APCsDiabetes developmentT cell-mediated autoimmune diseaseDiabetogenic CD8 T cellsCell-mediated autoimmune diseasePolymyxin BCD8 T cellsNonobese diabetic (NOD) miceType 1 diabetesHost immune systemIslet β-cellsAutoimmune diabetesDifferent time pointsImmune toleranceDiabetic miceAutoimmune diseasesProfound protectionT cellsImmune responseProtective effectCommensal microbiotaGut microbiotaSusceptible individualsCommensal bacteria
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 resultsActivation 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 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 peptideCellsPeptidesCytotoxicityAPLAssaysCD4CD86 Has Sustained Costimulatory Effects on CD8 T Cells
Thomas IJ, de Marquesini L, Ravanan R, Smith RM, Guerder S, Flavell RA, Wraith DC, Wen L, Wong FS. CD86 Has Sustained Costimulatory Effects on CD8 T Cells. The Journal Of Immunology 2007, 179: 5936-5946. PMID: 17947667, PMCID: PMC2629533, DOI: 10.4049/jimmunol.179.9.5936.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsB7-1 AntigenB7-2 AntigenCD8-Positive T-LymphocytesCell DifferentiationCell ProliferationCells, CulturedCytokinesDiabetes MellitusGene Expression RegulationHealthHumansIslets of Langerhans TransplantationMiceMice, TransgenicPromoter Regions, GeneticRatsReceptor, InsulinSurvival RateTime FactorsTransgenesConceptsCD8 T cellsT cellsT cell activationCD86 costimulationCell activationCytotoxic T-cell activationTransfer of diabetesOld NOD miceInhibitory molecule expressionRat insulin promoterGreater sustained activityNOD isletsRecurrent diabetesNOD miceDiabetes onsetDiabetic miceCostimulatory moleculesCTLA-4Cytokine secretionMolecule expressionCostimulatory effectImmune responseCD80CD86CD80 costimulationActivated 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
2005
The Influence of the Major Histocompatibility Complex on Development of Autoimmune Diabetes in RIP-B7.1 Mice
Wong FS, Du W, Thomas IJ, Wen L. The Influence of the Major Histocompatibility Complex on Development of Autoimmune Diabetes in RIP-B7.1 Mice. Diabetes 2005, 54: 2032-2040. PMID: 15983204, DOI: 10.2337/diabetes.54.7.2032.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsB7-1 AntigenCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesDiabetes Mellitus, Type 1Histocompatibility Antigens Class IHistocompatibility Antigens Class IIIslets of LangerhansLymphocyte DepletionMajor Histocompatibility ComplexMiceMice, Inbred C57BLMice, Inbred NODMice, SCIDConceptsT cell repertoireMajor histocompatibility complexI-Ag7Autoimmune T cell repertoireImportant genetic susceptibility factorAutoreactive T cell repertoireBALB/c miceHistocompatibility complexNonobese-resistant miceRIP-B7.1 miceCD8 T cellsNonobese diabetic (NOD) miceMHC class II moleculesDiabetes-resistant miceType 1 diabetesIslet beta cellsClass II moleculesCostimulatory molecule B7.1MHC class IC57BL/6 genetic backgroundGenetic susceptibility factorsLocal costimulationAutoimmune diabetesNOD miceSpontaneous diabetes
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
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