2025
Latent EBV enhances the efficacy of anti-CD3 mAb in Type 1 diabetes
Lledó-Delgado A, Preston-Hurlburt P, Higdon L, Hu A, James E, Lim N, Long S, McNamara J, Nguyen H, Serti E, Sumida T, Herold K. Latent EBV enhances the efficacy of anti-CD3 mAb in Type 1 diabetes. Nature Communications 2025, 16: 5033. PMID: 40447640, PMCID: PMC12125364, DOI: 10.1038/s41467-025-60276-5.Peer-Reviewed Original ResearchConceptsCD8+ T cellsEBV-seropositive individualsType 1 diabetesT cellsImmune cellsAntigen-specific CD8+ T cellsDiagnosis of type 1 diabetesEBV-seronegative patientsEBV-seropositive patientsT cell activation pathwaysRegulatory T cellsAnti-CD3 mAbInnate immune cellsPeripheral blood cellsT cell receptorProgression of diseaseContext of type 1 diabetesImpaired signaling pathwaysTeplizumabClinical trialsLatent EBVBlood cellsSingle cell transcriptomicsModulate progressionMTOR signaling
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 genes70-OR: PROTECT Per-Protocol Analysis—Preserving ß-Cell Function in Children and Adolescents with Newly Diagnosed Stage 3 Type 1 Diabetes (T1D)
HEROLD K, DAYAN C, CHATENOUD L, GITELMAN S, SUMNIK Z, SIMMONS K, SZYPOWSKA A, KNECHT L, NIEMOELLER E, TIAN W, RAMOS E. 70-OR: PROTECT Per-Protocol Analysis—Preserving ß-Cell Function in Children and Adolescents with Newly Diagnosed Stage 3 Type 1 Diabetes (T1D). Diabetes 2024, 73 DOI: 10.2337/db24-70-or.Peer-Reviewed Original ResearchIntent-to-treatInsulin doseFunction preservationPer-protocolIntent-to-treat populationSs-cell functionAnti-CD3 mAbReduced insulin doseLower insulin doseSustained glycemic controlPP populationTeplizumabMetabolic outcomesPBO groupHbA1c levelsPP analysisGlycemic controlTreatment complianceDoseDelayed onsetRandomized participantsIncorrect treatmentInsulinWeeksTreatmentReshaping 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-riskSingle-cell transcriptomics of CD8 T cells in autoimmune diabetes after anti-CD3 monoclonal antibody treatment
Wu Y, Spurrell M, Deng S, Herold K. Single-cell transcriptomics of CD8 T cells in autoimmune diabetes after anti-CD3 monoclonal antibody treatment. The Journal Of Immunology 2024, 212: 0998_4625-0998_4625. DOI: 10.4049/jimmunol.212.supp.0998.4625.Peer-Reviewed Original ResearchPancreas-draining lymph nodesIslet-infiltrating CD8 T cellsCD8 T cellsPre-diabetic NODAnti-CD3 mAbDiverse TCR repertoireT cellsNOD miceTCR repertoireTCF-1Pre-diabetic NOD miceImmune mediated destructionDiabetic NOD miceMonoclonal antibody treatmentLong-term toleranceExpression of EomesExpression of TCF-1Expression of TOXFragments of mAbsDelay type 1 diabetesType 1 diabetesAnti-CD3Autoimmune diabetesAntibody treatmentLymph nodes
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