2018
Treatment of type 1 diabetes with teplizumab: clinical and immunological follow-up after 7 years from diagnosis
Perdigoto AL, Preston-Hurlburt P, Clark P, Long SA, Linsley PS, Harris KM, Gitelman SE, Greenbaum CJ, Gottlieb PA, Hagopian W, Woodwyk A, Dziura J, Herold KC. Treatment of type 1 diabetes with teplizumab: clinical and immunological follow-up after 7 years from diagnosis. Diabetologia 2018, 62: 655-664. PMID: 30569273, PMCID: PMC6402971, DOI: 10.1007/s00125-018-4786-9.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAntibodies, Monoclonal, HumanizedArea Under CurveAutoimmunityCD3 ComplexCD8-Positive T-LymphocytesChildC-PeptideCytokinesDiabetes Mellitus, Type 1FemaleFollow-Up StudiesHumansHypoglycemic AgentsInsulinIslets of LangerhansMaleRandomized Controlled Trials as TopicRemission InductionTreatment OutcomeYoung AdultConceptsC-peptide responseType 1 diabetesMixed meal tolerance testDetectable C-peptideC-peptideInsulin useTolerance testT cellsControl groupNew-onset type 1 diabetesPeripheral blood mononuclear cellsConclusions/interpretationThese findingsAnti-CD3 monoclonal antibodyDaily insulin useBlood mononuclear cellsDiagnosis of diabetesSuccessful immune therapiesOriginal control groupCell death proteinAnergic CD8ResultsFifty-sixImmune therapyInterpretationThese findingsMononuclear cellsCytokine release
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
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
2011
Synergistic Reversal of Type 1 Diabetes in NOD Mice With Anti-CD3 and Interleukin-1 Blockade Evidence of Improved Immune Regulation
Ablamunits V, Henegariu O, Hansen JB, Opare-Addo L, Preston-Hurlburt P, Santamaria P, Mandrup-Poulsen T, Herold KC. Synergistic Reversal of Type 1 Diabetes in NOD Mice With Anti-CD3 and Interleukin-1 Blockade Evidence of Improved Immune Regulation. Diabetes 2011, 61: 145-154. PMID: 22043003, PMCID: PMC3237664, DOI: 10.2337/db11-1033.Peer-Reviewed Original ResearchConceptsReversal of diabetesNOD miceIL-1raIL-1βIL-1 receptor antagonistAnti-CD3 monoclonal antibodyCombination-treated miceIgG1 isotype antibodiesPancreatic lymph nodesMore IL-10Hyperglycemic NOD miceType 1 diabetesEffect of treatmentIntrapancreatic expressionSynergistic reversalAutoimmune diabetesIsotype antibodiesAdoptive transferIL-17Dendritic cellsIL-10Lymph nodesPersistent remissionIslet inflammationIL-6NKG2A is a marker for acquisition of regulatory function by human CD8+ T cells activated with anti‐CD3 antibody
Ablamunits V, Henegariu O, Preston‐Hurlburt P, Herold KC. NKG2A is a marker for acquisition of regulatory function by human CD8+ T cells activated with anti‐CD3 antibody. European Journal Of Immunology 2011, 41: 1832-1842. PMID: 21538351, PMCID: PMC3517122, DOI: 10.1002/eji.201041258.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalBiomarkersCD3 ComplexCD8-Positive T-LymphocytesGene ExpressionHumansInterleukin-2 Receptor alpha SubunitLymphocyte ActivationMicroarray AnalysisNK Cell Lectin-Like Receptor Subfamily CPolymerase Chain ReactionProtein IsoformsReceptors, Tumor Necrosis Factor, Type IIT-Lymphocytes, RegulatoryConceptsT cellsHuman CD8Response of CD8Induction of CD8Inhibitory receptor NKG2AType 1 diabetesAnti-CD3 mAbAnti-CD3 antibodyAcquisition of CD8NKG2A expressionTreg activityTreg inductionDrug therapyCD8TregsImmune responseNKG2ARegulatory functionsNegative signalingMarkersInductionCellsNegative markersDiabetesPatients