2024
Regulatory CD4+ T cells redirected against pathogenic CD8+ T cells protect NOD mice from development of autoimmune diabetes
Kakabadse D, Chen D, Fishman S, Weinstein-Marom H, Davies J, Wen L, Gross G, Wong F. Regulatory CD4+ T cells redirected against pathogenic CD8+ T cells protect NOD mice from development of autoimmune diabetes. Frontiers In Immunology 2024, 15: 1463971. PMID: 39351219, PMCID: PMC11439686, DOI: 10.3389/fimmu.2024.1463971.Peer-Reviewed Original ResearchCD8+ T cellsCD4+ T cellsAntigen-specific CD8+ T cellsDevelopment of autoimmune diabetesRegulatory T cellsCo-transfer experimentsT cellsNOD miceAutoimmune diabetesAntigen-specific CD4+ T cellsRegulatory CD4+ T cellsAntigen-specific cytotoxic CD8Pathogenic CD8+ T cellsPre-diabetic NOD micePolyclonal CD4+ T cellsDevelopment of type 1 diabetesSuppresses autoimmune diabetesAntigen-specific CD4Expression of Foxp3Young NOD miceT cell-T cellMarkers in vitroType 1 diabetesAdoptive transferTreg cells
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 cellsThe role of TLR3 in protection of diabetes by PolyI:C in NOD mice (136.31)
Xiang Y, Wen L, Zhou Z, Wong F. The role of TLR3 in protection of diabetes by PolyI:C in NOD mice (136.31). The Journal Of Immunology 2010, 184: 136.31-136.31. DOI: 10.4049/jimmunol.184.supp.136.31.Peer-Reviewed Original ResearchRole of TLR3Adoptive transferProtective effectDiabetes developmentNon-hematopoietic cellsNOD micePoly IYoung WTBone marrow chimera experimentsOnset of diabetesAdoptive transfer modelExpression of TLR3Diabetic wild typeC administrationTLR3Chimera experimentsPolyIMiceRecipientsTreatmentDiabetesDisease developmentExogenous treatmentNODCells
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
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
2003
Critical roles of CD30/CD30L interactions in murine autoimmune diabetes
CHAKRABARTY S, NAGATA M, YASUDA H, WEN L, NAKAYAMA M, CHOWDHURY S, YAMADA K, JIN Z, KOTANI R, MORIYAMA H, SHIMOZATO O, YAGITA H, YOKONO K. Critical roles of CD30/CD30L interactions in murine autoimmune diabetes. Clinical & Experimental Immunology 2003, 133: 318-325. PMID: 12930356, PMCID: PMC1808783, DOI: 10.1046/j.1365-2249.2003.02223.x.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsAntibodies, MonoclonalAutoimmune DiseasesCD30 LigandCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesDiabetes Mellitus, ExperimentalFemaleIslets of LangerhansKi-1 AntigenMaleMembrane GlycoproteinsMiceMice, Inbred NODMice, SCIDT-LymphocytesT-Lymphocytes, CytotoxicConceptsCD30/CD30L interactionIslet-specific CD4NOD miceDevelopment of diabetesT cell linesAutoimmune diabetesDiabetic NOD miceSpontaneous autoimmune diabetesPancreatic lymph nodesYoung NOD miceNOD-SCID miceT cell proliferationCD30/CD30LTumor necrosis factor receptorWeeks of ageCell linesNecrosis factor receptorMurine autoimmuneIslet antigensSpontaneous diabetesAdoptive transferLymph nodesEffector phaseT cellsSpleen cells
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