2024
Single-cell transcriptomics of CD8 T cells in autoimmune diabetes after anti-CD3 monoclonal antibody treatment
Wu Y, Spurrell M, Deng S, Herold K. Single-cell transcriptomics of CD8 T cells in autoimmune diabetes after anti-CD3 monoclonal antibody treatment. The Journal Of Immunology 2024, 212: 0998_4625-0998_4625. DOI: 10.4049/jimmunol.212.supp.0998.4625.Peer-Reviewed Original ResearchPancreas-draining lymph nodesIslet-infiltrating CD8 T cellsCD8 T cellsPre-diabetic NODAnti-CD3 mAbDiverse TCR repertoireT cellsNOD miceTCR repertoireTCF-1Pre-diabetic NOD miceImmune mediated destructionDiabetic NOD miceMonoclonal antibody treatmentLong-term toleranceExpression of EomesExpression of TCF-1Expression of TOXFragments of mAbsDelay type 1 diabetesType 1 diabetesAnti-CD3Autoimmune diabetesAntibody treatmentLymph nodes
2022
Immune cells and their inflammatory mediators modify beta cells and cause checkpoint inhibitor-induced diabetes
Perdigoto AL, Deng S, Du KC, Kuchroo M, Burkhardt DB, Tong A, Israel G, Robert ME, Weisberg SP, Kirkiles-Smith N, Stamatouli AM, Kluger HM, Quandt Z, Young A, Yang ML, Mamula MJ, Pober JS, Anderson MS, Krishnaswamy S, Herold KC. Immune cells and their inflammatory mediators modify beta cells and cause checkpoint inhibitor-induced diabetes. JCI Insight 2022, 7: e156330. PMID: 35925682, PMCID: PMC9536276, DOI: 10.1172/jci.insight.156330.Peer-Reviewed Original ResearchConceptsCheckpoint inhibitorsΒ-cellsPD-1/PD-L1 pathwayT-lymphocyte antigen-4PD-1 blockadePD-L1 pathwayDeath ligand 1NOD mouse modelDevelopment of diabetesHuman β-cellsAutoimmune complicationsNOD miceΒ-cell populationDeath-1Diabetes mellitusImmune infiltratesInflammatory mediatorsPancreatic inflammationPD-L1Induced diabetesLymphocytic infiltrationInflammatory cytokinesAntigen-4Immune cellsT cells
2017
β Cells that Resist Immunological Attack Develop during Progression of Autoimmune Diabetes in NOD Mice
Rui J, Deng S, Arazi A, Perdigoto AL, Liu Z, Herold KC. β Cells that Resist Immunological Attack Develop during Progression of Autoimmune Diabetes in NOD Mice. Cell Metabolism 2017, 25: 727-738. PMID: 28190773, PMCID: PMC5342930, DOI: 10.1016/j.cmet.2017.01.005.Peer-Reviewed Original ResearchConceptsΒ-cellsImmune attackNon-obese diabetic (NOD) miceImmune inhibitory markersProgression of T1DChronic autoimmune diseaseType 1 diabetesLong-term survivalNormal β-cellsHuman β-cellsIslet infiltratesAutoimmune diabetesNOD miceDiabetic miceAutoimmune diseasesInhibitory markersImmune cellsImmune responseDiabetesStemness genesΒ cell identity genesSimilar changesCell deathDiseaseMice
2016
Characterization of Diabetogenic CD8+ T Cells IMMUNE THERAPY WITH METABOLIC BLOCKADE*
Garyu JW, Uduman M, Stewart A, Rui J, Deng S, Shenson J, Staron MM, Kaech SM, Kleinstein SH, Herold KC. Characterization of Diabetogenic CD8+ T Cells IMMUNE THERAPY WITH METABOLIC BLOCKADE*. Journal Of Biological Chemistry 2016, 291: 11230-11240. PMID: 26994137, PMCID: PMC4900270, DOI: 10.1074/jbc.m115.713362.Peer-Reviewed Original ResearchConceptsPrediabetic NOD miceNOD miceT cellsDiabetogenic CD8Reactive cellsMemory precursor effector cellsType 1 diabetes mellitusΒ-cellsGlucose tolerance deterioratesAutoreactive T cellsHyperglycemic NOD miceInsulin-producing β-cellsAutoimmune effectorsAutoimmune diabetesReactive CD8Glucose intoleranceDiabetes mellitusEffector cellsImmune therapyMetabolic disturbancesTolerance deterioratesDisease progressionInsulin pelletsSubset of cellsConventional antigensMethylation of insulin DNA in response to proinflammatory cytokines during the progression of autoimmune diabetes in NOD mice
Rui J, Deng S, Lebastchi J, Clark PL, Usmani-Brown S, Herold KC. Methylation of insulin DNA in response to proinflammatory cytokines during the progression of autoimmune diabetes in NOD mice. Diabetologia 2016, 59: 1021-1029. PMID: 26910463, PMCID: PMC4826795, DOI: 10.1007/s00125-016-3897-4.Peer-Reviewed Original ResearchConceptsInsulin gene expressionGene expressionQuantitative real-time RT-PCRMethylation marksInsulin geneNOD miceBeta cellsDNA methyltransferasesDisease progressionAims/hypothesisType 1 diabetesIns2 geneInsulin DNAMethylationReal-time RT-PCRGenesBeta-cell functionExon 1Human beta cellsBeta-cell massPancreatic beta cellsType 1 diabetesMethyltransferasesEffects of cytokinesExon 2Cell mass
2015
A Preclinical Consortium Approach for Assessing the Efficacy of Combined Anti-CD3 Plus IL-1 Blockade in Reversing New-Onset Autoimmune Diabetes in NOD Mice
Gill RG, Pagni PP, Kupfer T, Wasserfall CH, Deng S, Posgai A, Manenkova Y, Hani A, Straub L, Bernstein P, Atkinson MA, Herold KC, von Herrath M, Staeva T, Ehlers MR, Nepom GT. A Preclinical Consortium Approach for Assessing the Efficacy of Combined Anti-CD3 Plus IL-1 Blockade in Reversing New-Onset Autoimmune Diabetes in NOD Mice. Diabetes 2015, 65: 1310-1316. PMID: 26718498, PMCID: PMC5860426, DOI: 10.2337/db15-0492.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalAutoimmune DiseasesBiomedical ResearchCD3 ComplexDiabetes Mellitus, Type 1Drug Administration ScheduleDrug Therapy, CombinationFemaleImmunoglobulin Fab FragmentsImmunotherapyInsulinInsulin SecretionInsulin-Secreting CellsInterleukin-1 Receptor Accessory ProteinInterleukin-1betaMice, Inbred NODMulticenter Studies as TopicPilot ProjectsReceptors, Interleukin-1 Type IRecombinant Fusion ProteinsReproducibility of ResultsResearch DesignSpecific Pathogen-Free OrganismsUnited StatesConceptsNew-onset diseaseIL-1 blockadeAnti-CD3 treatmentNOD micePreclinical studiesInterleukin-1IL-1β monoclonal antibodyIslet β-cell massNOD mouse modelImmune Tolerance NetworkType 1 diabetesΒ-cell massApplicable immunotherapiesFuture clinical useStudy entryProspective studyClinical trialsMouse modelMulticenter consortiumAnimal modelsCandidate therapeuticsClinical useTherapeutic agentsMonoclonal antibodiesDisease
2008
Anti‐CD20 Treatment Prolongs Syngeneic Islet Graft Survival and Delays the Onset of Recurrent Autoimmune Diabetes
Hu C, Deng S, Wong FS, Wen L. Anti‐CD20 Treatment Prolongs Syngeneic Islet Graft Survival and Delays the Onset of Recurrent Autoimmune Diabetes. Annals Of The New York Academy Of Sciences 2008, 1150: 217-219. PMID: 19120299, DOI: 10.1196/annals.1447.032.Peer-Reviewed Original ResearchConceptsImmunosuppressive drug treatmentType 1 diabetesIslet transplantationDrug treatmentLong-term immunosuppressive drug treatmentSyngeneic islet graft survivalB cell depletion therapyT cell-mediated destructionAccepted therapeutic optionB-cell depletionPancreatic islet beta cellsCell-mediated destructionIslet graft survivalSyngeneic islet transplantationPancreatic islet transplantationIslet beta cellsRecurrent AutoimmuneTolerance establishmentGraft survivalNOD miceTherapeutic optionsAutoimmune diseasesCell depletionInsulin treatmentBeta cells