2017
Microbiota control immune regulation in humanized mice
Gülden E, Vudattu NK, Deng S, Preston-Hurlburt P, Mamula M, Reed JC, Mohandas S, Herold BC, Torres R, Vieira SM, Lim B, Herazo-Maya JD, Kriegel M, Goodman AL, Cotsapas C, Herold KC. Microbiota control immune regulation in humanized mice. JCI Insight 2017, 2: e91709. PMID: 29093268, PMCID: PMC5752290, DOI: 10.1172/jci.insight.91709.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAnimalsAntibodies, AntinuclearAntibodies, Monoclonal, HumanizedAutoimmune DiseasesB7-2 AntigenCD11b AntigenCD11c AntigenCD3 ComplexCD8-Positive T-LymphocytesCytokinesDisease Models, AnimalGastrointestinal MicrobiomeGastrointestinal TractGraft RejectionHumansImmunosuppressive AgentsImmunotherapyInterferon-gammaInterleukin-10Interleukin-27Leukocytes, MononuclearMiceMice, KnockoutMucous MembraneSkin TransplantationSTAT5 Transcription FactorT-LymphocytesTransplantation, HeterologousConceptsT cellsIL-10Humanized miceHuman peripheral blood mononuclear cellsPeripheral blood mononuclear cellsIL-27 expressionIL-10 levelsAnti-nuclear antibodiesEffector T cellsLevels of IFNCentral memory cellsLess IL-10Markers of efficacyBlood mononuclear cellsExpression of CD86Immune regulatory pathwaysIL-10 inductionHuman immune cellsHuman stool samplesImmunosuppressive medicationsIL-27Xenograft rejectionImmune therapyMononuclear cellsAntibiotic treatmentOral treatment with foralumab, a fully human anti-CD3 monoclonal antibody, prevents skin xenograft rejection in humanized mice
Ogura M, Deng S, Preston-Hurlburt P, Ogura H, Shailubhai K, Kuhn C, Weiner HL, Herold KC. Oral treatment with foralumab, a fully human anti-CD3 monoclonal antibody, prevents skin xenograft rejection in humanized mice. Clinical Immunology 2017, 183: 240-246. PMID: 28739191, DOI: 10.1016/j.clim.2017.07.005.Peer-Reviewed Original ResearchConceptsSkin xenograft rejectionOral treatmentXenograft rejectionT cellsAnti-CD3 monoclonal antibodyConsecutive daily dosesPeripheral T cellsActivation of splenocytesHuman immune systemSplenic CD8Graft acceptanceWeekly dosingIL-10Serum levelsImmune therapySmall bowelHumanized miceDaily dosesImmune modulationMucosal barrierIntragastric doseOral administrationSkin graftsProliferative responseLymphoid cells
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 antigens
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, HumanizedC-PeptideCD3 ComplexCytotoxicity 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
2012
Teplizumab Induces Human Gut-Tropic Regulatory Cells in Humanized Mice and Patients
Waldron-Lynch F, Henegariu O, Deng S, Preston-Hurlburt P, Tooley J, Flavell R, Herold KC. Teplizumab Induces Human Gut-Tropic Regulatory Cells in Humanized Mice and Patients. Science Translational Medicine 2012, 4: 118ra12. PMID: 22277969, PMCID: PMC4131554, DOI: 10.1126/scitranslmed.3003401.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, Monoclonal, HumanizedCD3 ComplexCell MovementDiabetes Mellitus, Type 1Forkhead Transcription FactorsGastrointestinal TractHumansHypoglycemic AgentsInterleukin-10Intestine, SmallL-SelectinMiceMucous MembraneNatalizumabOligonucleotide Array Sequence AnalysisReceptors, CCR6T-Lymphocytes, RegulatoryConceptsHumanized micePeripheral circulationSmall intestineType 1 diabetes mellitusNovel immunologic mechanismIL-10 expressionTreatment of patientsType 1 diabetesSecondary lymph organsHuman immune cellsT cell migrationMechanism of actionGut-tropicImmunologic mechanismsRegulatory cellsDiabetes mellitusImmune therapyInterleukin-10Immune cellsRegulatory cytokinesClinical trialsPreclinical modelsClinical studiesT cellsHuman hematopoietic stem cells