2020
The receptor for advanced glycation endproducts (RAGE) modulates T cell signaling
Reed JC, Preston-Hurlburt P, Philbrick W, Betancur G, Korah M, Lucas C, Herold KC. The receptor for advanced glycation endproducts (RAGE) modulates T cell signaling. PLOS ONE 2020, 15: e0236921. PMID: 32986722, PMCID: PMC7521722, DOI: 10.1371/journal.pone.0236921.Peer-Reviewed Original ResearchConceptsT cellsAdvanced glycation endproductsRAGE expressionGlycation endproductsType 1 diabetes mellitusLess IL-2T cell reactivityT-cell phenotypeHealthy control subjectsIL-2 productionT cell receptorPhosphorylation of ZAP70Human T cellsDiabetes mellitusAutoimmune diseasesJurkat cellsCell reactivityControl subjectsInflammatory productsIL-2Primary CD4T cell signalingCell receptorPatientsCell phenotype
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 releaseIdentification and Analysis of Islet Antigen–Specific CD8+ T Cells with T Cell Libraries
Ogura H, Preston-Hurlburt P, Perdigoto AL, Amodio M, Krishnaswamy S, Clark P, Yu H, Egli D, Fouts A, Steck AK, Herold KC. Identification and Analysis of Islet Antigen–Specific CD8+ T Cells with T Cell Libraries. The Journal Of Immunology 2018, 201: 1662-1670. PMID: 30082321, PMCID: PMC6449153, DOI: 10.4049/jimmunol.1800267.Peer-Reviewed Original ResearchMeSH KeywordsCD8-Positive T-LymphocytesDiabetes Mellitus, Type 1FemaleHumansInsulin-Secreting CellsMaleReceptors, Antigen, T-CellConceptsAg-specific T cellsT cellsT cell librariesIslet antigen-specific CD8Antigen-specific CD8Class I MHC tetramersAg-specific cellsT cell subsetsHealthy control subjectsType 1 diabetesT cell clonotypesTCR gene sequencesAutoreactive CD8Reactive CD8T1D patientsCell subsetsMHC tetramersPeripheral bloodControl subjectsHealthy controlsCell clonotypesCD8Activation phenotypePatientsTCR sequences
2016
The Receptor for Advanced Glycation Endproducts Drives T Cell Survival and Inflammation in Type 1 Diabetes Mellitus
Durning SP, Preston-Hurlburt P, Clark PR, Xu D, Herold KC, Group T. The Receptor for Advanced Glycation Endproducts Drives T Cell Survival and Inflammation in Type 1 Diabetes Mellitus. The Journal Of Immunology 2016, 197: 3076-3085. PMID: 27655844, PMCID: PMC5101164, DOI: 10.4049/jimmunol.1600197.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAsymptomatic DiseasesCD8-Positive T-LymphocytesCell SurvivalCells, CulturedChildDiabetes Mellitus, Type 1Disease ProgressionFemaleGene Expression ProfilingHumansImmunologic MemoryInflammationLymphocyte ActivationMaleReceptor for Advanced Glycation End ProductsRiskSignal TransductionUp-RegulationYoung AdultConceptsDamage-associated molecular patternsT cellsRAGE expressionT1D patientsInflammatory functionsRisk relativesCell activationHigh mobility group box 1Mobility group box 1Advanced glycated endproductsChronic autoimmune responseMolecular patternsEffector memory cellsHealthy control subjectsExpression of RAGEGroup box 1Type 1 diabetesAdvanced glycation endproductsT cell survivalAutoimmune responseAutoimmune diseasesControl subjectsDisease onsetRisk subjectsCell injury
2012
Enhanced Anti-Serpin Antibody Activity Inhibits Autoimmune Inflammation in Type 1 Diabetes
Czyzyk J, Henegariu O, Preston-Hurlburt P, Baldzizhar R, Fedorchuk C, Esplugues E, Bottomly K, Gorus FK, Herold K, Flavell RA. Enhanced Anti-Serpin Antibody Activity Inhibits Autoimmune Inflammation in Type 1 Diabetes. The Journal Of Immunology 2012, 188: 6319-6327. PMID: 22593614, PMCID: PMC3370061, DOI: 10.4049/jimmunol.1200467.Peer-Reviewed Original ResearchConceptsAutoimmune diabetes-prone NOD miceDiabetes-prone NOD miceHuman type 1 diabetesAnti-insulin autoantibodiesOnset of diabetesProtective humoral immunityType 1 diabetesNOD miceAutoimmune inflammationIslet inflammationNOD modelSuboptimal doseAutoimmune diseasesHumoral immunityImmunological toleranceT cellsHumoral activityType 1Early onsetDiabetesElevated levelsClade B serpinsAutoantibodiesInflammationProtease inhibitorsTeplizumab 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-6