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 genes
2023
HSV-2 triggers upregulation of MALAT1 in CD4+ T cells and promotes HIV latency reversal
Pierce C, Loh L, Steach H, Cheshenko N, Preston-Hurlburt P, Zhang F, Stransky S, Kravets L, Sidoli S, Philbrick W, Nassar M, Krishnaswamy S, Herold K, Herold B. HSV-2 triggers upregulation of MALAT1 in CD4+ T cells and promotes HIV latency reversal. Journal Of Clinical Investigation 2023, 133: e164317. PMID: 37079384, PMCID: PMC10232005, DOI: 10.1172/jci164317.Peer-Reviewed Original ResearchConceptsHIV-1 reactivationHIV latency reversalT cellsLatency reversalHuman CD4HIV-1 viral loadHIV-1 restriction factorsHSV-2 recurrencesHSV-2 infectionHIV-1 latencyUpregulation of MALAT1Primary human CD4HSV-2 proteinsViral loadHIV replicationPeripheral bloodMALAT1 expressionHSV-2Tissue reservoirsCD4Viral replicationExpression of transcriptsBystander cellsRestriction factorsMALAT1
2022
RAGE antagonism with azeliragon improves xenograft rejection by T cells in humanized mice.
Joshi AA, Wu Y, Deng S, Preston-Hurlburt P, Forbes JM, Herold KC. RAGE antagonism with azeliragon improves xenograft rejection by T cells in humanized mice. Clinical Immunology 2022, 245: 109165. PMID: 36257528, DOI: 10.1016/j.clim.2022.109165.Peer-Reviewed Original ResearchConceptsXenograft rejectionIL-17AHumanized miceIL-1βT cellsImmune responseRAGE antagonistsAdaptive human immune responsesPD-1 expressionSkin graft rejectionHuman immune cell responsesImmune cell responsesHuman immune responseHuman immune cellsInnate immune responseAdvanced glycation endproductsInhibition of pathwaysSmall molecule antagonistsMultiple inflammatory processesAZ therapyRAGE antagonismGraft rejectionIL-23Serum levelsMedian timeHSV-2 increases replication of HIV in human T cells
Pierce C, Preston-Hurlburt P, Loh L, Steach H, Sidoli S, Zhang F, Philbrick W, Nassar M, Krishnaswamy S, Herold K, Herold B. HSV-2 increases replication of HIV in human T cells. The Journal Of Immunology 2022, 208: 182.40-182.40. DOI: 10.4049/jimmunol.208.supp.182.40.Peer-Reviewed Original ResearchCD4 cellsHSV-2HIV reactivationHIV PVLT cellsHerpes simplex virus 2 infectionLncRNA MALAT1Simplex virus 2 infectionHIV-LTR expressionHSV-2 lesionsMALAT1 gene expressionUninfected CD4 cellsFollicular helper cellsHSV-2 infectionCD4 T cellsHIV restriction factorsVirus 2 infectionGlobal HIV epidemicHSV-2 glycoprotein BHIV latent reservoirHuman T cellsInterferon response genesMucosal responsesHSV infectionLatent reservoir
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 phenotypeImmune responses to SARS-CoV-2 infection in hospitalized pediatric and adult patients
Pierce CA, Preston-Hurlburt P, Dai Y, Aschner CB, Cheshenko N, Galen B, Garforth SJ, Herrera NG, Jangra RK, Morano NC, Orner E, Sy S, Chandran K, Dziura J, Almo SC, Ring A, Keller MJ, Herold KC, Herold BC. Immune responses to SARS-CoV-2 infection in hospitalized pediatric and adult patients. Science Translational Medicine 2020, 12: eabd5487. PMID: 32958614, PMCID: PMC7658796, DOI: 10.1126/scitranslmed.abd5487.Peer-Reviewed Original ResearchConceptsImmune responsePediatric patientsAntibody titersAdult patientsSerum concentrationsT cellsSevere acute respiratory syndrome coronavirus 2IFN-γ serum concentrationsAcute respiratory syndrome coronavirus 2Robust T cell responsesSARS-CoV-2 infectionAntibody-dependent cellular phagocytosisRespiratory syndrome coronavirus 2Frequency of IFNMultisystem inflammatory syndromeT cell responsesCellular immune responsesSyndrome coronavirus 2Adaptive immune responsesAntiviral immune responseTumor necrosis factorMetropolitan hospital systemCoronavirus disease 2019COVID-19Age-dependent factorsUse of CART cells to selectively target autoantigen-specific T cells for the treatment of autoimmune diabetes
Yu H, Bettini M, Ellis G, Riley J, Collins J, Preston-Hurlburt P, Korah M, Mallone R, Deng S, Wang X, Fremont D, Spiegel D, Cresswell P, Herold K. Use of CART cells to selectively target autoantigen-specific T cells for the treatment of autoimmune diabetes. The Journal Of Immunology 2020, 204: 238.8-238.8. DOI: 10.4049/jimmunol.204.supp.238.8.Peer-Reviewed Original ResearchCART cellsT cellsAutoimmune diabetesCAR constructsHuman antigen-specific CD8Autoantigen-specific T cellsAntigen-specific CD8Pathogenic T cellsPrevious clinical trialsΒ-cell damageChimeric antigen receptorNon-specific actionT cell linesHuman T cellsDominant cell typeHuman insulitisPathogenic subpopulationsNovel immunotherapiesPrimary human T cellsClinical trialsPrimary mediatorPeptide epitopesAntigen receptorMicroglobulin complexCAR signalingHSV-2 infects T follicular helper cells to promote HIV reactivation
Pierce C, Loh L, Preston-Hurlburt P, Herold K, Herold B. HSV-2 infects T follicular helper cells to promote HIV reactivation. The Journal Of Immunology 2020, 204: 247.24-247.24. DOI: 10.4049/jimmunol.204.supp.247.24.Peer-Reviewed Original ResearchCD4 T cellsFollicular helper cellsHIV reactivationHSV-2T cellsTfh cellsIL-32Helper cellsSystemic effectsCD4 T-cell subpopulationsT Follicular Helper CellsHSV-2 recurrencesHSV-2 seropositiveT cell subpopulationsGlobal HIV epidemicPotential systemic effectsT cell linesSeronegative womenIL-32γHigh HIVViral loadHIV transmissionLatent HIVProinflammatory cytokinesHIV epidemic
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
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
Role of Interleukin 32 in Human Immunodeficiency Virus Reactivation and Its Link to Human Immunodeficiency Virus–Herpes Simplex Virus Coinfection
Mesquita PM, Preston-Hurlburt P, Keller MJ, Vudattu N, Espinoza L, Altrich M, Anastos K, Herold KC, Herold BC. Role of Interleukin 32 in Human Immunodeficiency Virus Reactivation and Its Link to Human Immunodeficiency Virus–Herpes Simplex Virus Coinfection. The Journal Of Infectious Diseases 2016, 215: 614-622. PMID: 28007920, PMCID: PMC5388286, DOI: 10.1093/infdis/jiw612.Peer-Reviewed Original ResearchMeSH KeywordsAdultCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCoinfectionCore Binding Factor Alpha 2 SubunitCross-Sectional StudiesDNA, ViralFemaleHerpes GenitalisHerpesvirus 2, HumanHIV InfectionsHIV-1HumansInterleukinsLeukocytes, MononuclearMiddle AgedRecombinant ProteinsRNA, ViralViral LoadYoung AdultConceptsHuman immunodeficiency virus type 1T cellsIL-32HSV-2HIV reactivationHIV reservoirHIV DNACell-associated HIV DNAHuman Immunodeficiency Virus ReactivationHerpes simplex virus type 2Peripheral blood mononuclear cellsSimplex virus type 2Immunodeficiency virus type 1Frequency of CCR5Higher HIV DNARecombinant IL-32γSystemic T cellsRUNX1 inhibitorT-cell phenotypeBlood mononuclear cellsSubpopulation of CD4Virus type 1Virus type 2Interleukin-32γAntiretroviral therapyThe 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
2014
Humanized Mice as a Model for Aberrant Responses in Human T Cell Immunotherapy
Vudattu NK, Waldron-Lynch F, Truman LA, Deng S, Preston-Hurlburt P, Torres R, Raycroft MT, Mamula MJ, Herold KC. Humanized Mice as a Model for Aberrant Responses in Human T Cell Immunotherapy. The Journal Of Immunology 2014, 193: 587-596. PMID: 24943216, PMCID: PMC4123131, DOI: 10.4049/jimmunol.1302455.Peer-Reviewed Original ResearchMeSH KeywordsAdrenal GlandsAnimalsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAutoimmune DiseasesCytokinesDisease Models, AnimalFlow CytometryHumansInterleukin Receptor Common gamma SubunitIpilimumabLiverLymphocyte ActivationMacrophagesMiceMice, Inbred NODMice, KnockoutMice, SCIDPhosphorylationSTAT5 Transcription FactorStem Cell TransplantationSurvival AnalysisT-LymphocytesT-Lymphocytes, RegulatoryTransplantation, HeterologousWeight LossConceptsAnti-nuclear AbsAutoimmune diseasesRegulatory cellsHumanized miceT cellsImmune responseWeight lossMesenteric lymph nodesHuman autoimmune diseasesInduction of autoimmunityT-cell immunotherapyRelease of IFNHuman immune responseImmune-deficient miceIpilimumab treatmentInflammatory sequelaeLymph nodesCell immunotherapyIP-10Macrophage infiltrationCytokine productionSpleen cellsPathologic processesHepatitisMiceThe Receptor for Advanced Glycation End Products (RAGE) Affects T Cell Differentiation in OVA Induced Asthma
Akirav EM, Henegariu O, Preston-Hurlburt P, Schmidt AM, Clynes R, Herold KC. The Receptor for Advanced Glycation End Products (RAGE) Affects T Cell Differentiation in OVA Induced Asthma. PLOS ONE 2014, 9: e95678. PMID: 24759895, PMCID: PMC3997417, DOI: 10.1371/journal.pone.0095678.Peer-Reviewed Original ResearchConceptsAdaptive immune responsesT cell responsesEffects of RAGEGlycation end productsT cell activationT cellsImmune responseWT miceCellular infiltrationCell activationCell responsesBronchial alveolar lavage fluidAdvanced glycation end productsMediastinal lymph nodesT cell infiltrationIL-5 productionOT-II miceRAGE-deficient miceT cell subsetsAlveolar lavage fluidMultiplex bead analysisRole of RAGET cell proliferationDeficient T cellsT cell differentiation
2012
Analysis of Human Biologics With a Mouse Skin Transplant Model in Humanized Mice
Waldron-Lynch F, Deng S, Preston-Hurlburt P, Henegariu O, Herold KC. Analysis of Human Biologics With a Mouse Skin Transplant Model in Humanized Mice. American Journal Of Transplantation 2012, 12: 2652-2662. PMID: 22900715, DOI: 10.1111/j.1600-6143.2012.04178.x.Peer-Reviewed Original ResearchConceptsSkin transplant modelGraft rejectionTransplant modelHumanized miceSkin graftsT cellsFunctional human immune responsesMouse skin transplant modelMurine skin transplant modelCentral memory T cellsNOD/SCID/Mouse skin graftsMemory T cellsMonoclonal antibody therapySkin graft rejectionDevelopment of effectorHuman immune responseMHC class IHuman T cellsIpilimumab treatmentAntibody therapySCID/Diffuse infiltrationMouse donorsSerum immunoglobulinsEnhanced 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 inhibitorsRAGE Expression in Human T Cells: A Link between Environmental Factors and Adaptive Immune Responses
Akirav EM, Preston-Hurlburt P, Garyu J, Henegariu O, Clynes R, Schmidt AM, Herold KC. RAGE Expression in Human T Cells: A Link between Environmental Factors and Adaptive Immune Responses. PLOS ONE 2012, 7: e34698. PMID: 22509345, PMCID: PMC3324532, DOI: 10.1371/journal.pone.0034698.Peer-Reviewed Original ResearchConceptsHuman immune responseT cellsImmune responseHuman T cellsRAGE expressionAntigen-specific T cellsAdaptive human immune responsesAdaptive immune cellsSpecific T cellsHealthy control subjectsAdaptive immune responsesExpression of RAGELevels of RAGEInnate immune responseAdvanced glycation endproductsActivated T cellsT cell activationIL-17AGlucose controlControl subjectsIL-5Immune cellsGlycation endproductsCell activationPatientsTeplizumab 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