2024
Teplizumab induces persistent changes in the antigen‐specific repertoire in individuals at‐risk for type 1 diabetes
Lledó-Delgado A, Preston-Hurlburt P, Currie S, Clark P, Linsley P, Long S, Liu C, Koroleva G, Martins A, Tsang J, Herold K. Teplizumab induces persistent changes in the antigen‐specific repertoire in individuals at‐risk for type 1 diabetes. Journal Of Clinical Investigation 2024, 134: e177492. PMID: 39137044, PMCID: PMC11405034, DOI: 10.1172/jci177492.Peer-Reviewed Original ResearchCD8+ T cellsAutoreactive T cellsT cellsType 1 diabetesPeripheral blood CD8+ T cellsBlood CD8+ T cellsExpansion of autoreactive T cellsOperational toleranceExpression of CD127Progression of type 1 diabetesAnti-CD3 mAbAntigen-specific repertoireT cell receptorAt-risk patientsAnalysis of study participantsStudy participantsIL7R expressionTeplizumab groupCD8+Placebo groupCD4+Clinical respondersFree intervalTeplizumabReduced expression of genesReshaping immune cells and the antigen-specific repertoire by anti-CD3 mAb teplizumab in Type 1 diabetes
lledo delgado A, Preston-Hurlburt P, Currie S, Clark P, Herold K. Reshaping immune cells and the antigen-specific repertoire by anti-CD3 mAb teplizumab in Type 1 diabetes. The Journal Of Immunology 2024, 212: 0958_5059-0958_5059. DOI: 10.4049/jimmunol.212.supp.0958.5059.Peer-Reviewed Original ResearchCD8+ T cellsT cellsType 1 diabetesCD8+ T cell exhaustionAutoreactive CD8+ T cellsT cell exhaustionT cell changesCD8+ cellsProgression of type 1 diabetesAnti-CD3 mAbAntigen-specific repertoireAt-risk patientsCD8+CD4+Eomes expressionPeripheral bloodTeplizumabImmune cellsImmune regulationT1D diagnosisCD8Operational toleranceDelay progressionMonthsIndividuals at-risk
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 ResearchConceptsAg-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
2013
Specific peripheral B cell tolerance defects in patients with multiple sclerosis
Kinnunen T, Chamberlain N, Morbach H, Cantaert T, Lynch M, Preston-Hurlburt P, Herold KC, Hafler DA, O’Connor K, Meffre E. Specific peripheral B cell tolerance defects in patients with multiple sclerosis. Journal Of Clinical Investigation 2013, 123: 2737-2741. PMID: 23676463, PMCID: PMC3668812, DOI: 10.1172/jci68775.Peer-Reviewed Original ResearchConceptsB cell tolerance checkpointsB cell tolerance defectsMultiple sclerosisRheumatoid arthritisTolerance checkpointsB cellsPeripheral B cell tolerance checkpointsTolerance defectsAutoreactive B cell clonesMature naive B cellsType 1 diabetesAutoreactive B cellsB cell toleranceCentral nervous systemNaive B cellsB cell clonesB cell selectionEarly B cell developmentIPEX patientsMost patientsTreg functionHomeostatic proliferationAutoimmune diseasesPatientsHealthy individuals
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-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