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
2013
Immune Therapy and β-Cell Death in Type 1 Diabetes
Lebastchi J, Deng S, Lebastchi AH, Beshar I, Gitelman S, Willi S, Gottlieb P, Akirav EM, Bluestone JA, Herold KC. Immune Therapy and β-Cell Death in Type 1 Diabetes. Diabetes 2013, 62: 1676-1680. PMID: 23423576, PMCID: PMC3636605, DOI: 10.2337/db12-1207.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntibodies, Monoclonal, HumanizedCD3 ComplexC-PeptideCytotoxicity Tests, ImmunologicCytotoxicity, ImmunologicDiabetes Mellitus, Type 1DNA MethylationFemaleHumansHypoglycemic AgentsImmunologic FactorsImmunotherapyInsulinInsulin SecretionInsulin-Secreting CellsIslets of LangerhansMalePostprandial PeriodYoung AdultConceptsRecent-onset T1DΒ-cell deathΒ-cellsNondiabetic subjectsImmune therapyType 1 diabetes resultsAnti-CD3 monoclonal antibodyUnmethylated INS DNAC-peptide responseNondiabetic control subjectsΒ-cell functionInsulin-producing β-cellsHigh rateImmune interventionDiabetes resultsControl subjectsClinical trialsPatientsT1DType 1Monoclonal antibodiesDeathTeplizumabINS DNATherapy