Latent EBV enhances the efficacy of anti-CD3 mAb in Type 1 diabetes

Ana Lledó-Delgado, Paula Preston-Hurlburt, Lauren Higdon, Alex Hu, Eddie James, Noha Lim, S. Alice Long, James McNamara, Hai Nguyen, Elisavet Serti, Tomokazu S. Sumida and Kevan C. Herold ()
Additional contact information
Ana Lledó-Delgado: Yale University School of Medicine
Paula Preston-Hurlburt: Yale University School of Medicine
Lauren Higdon: Immune Tolerance Network
Alex Hu: Benaroya Research Institute at Virginia Mason
Eddie James: Benaroya Research Institute at Virginia Mason
Noha Lim: Immune Tolerance Network
S. Alice Long: Benaroya Research Institute at Virginia Mason
James McNamara: National Institutes of Health
Hai Nguyen: Benaroya Research Institute at Virginia Mason
Elisavet Serti: Immune Tolerance Network
Tomokazu S. Sumida: Yale University School of Medicine
Kevan C. Herold: Yale University School of Medicine

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: Abstract Teplizumab is approved for delaying the diagnosis of type 1 diabetes by modulating progression of disease. Compared to EBV-seronegative patients, those who are EBV-seropositive prior to treatment have a more robust response to teplizumab in two clinical trials. Here we compare the phenotypes, transcriptomes and development of peripheral blood cells before and after teplizumab treatment in participants. Higher number of regulatory T cells and partially exhausted CD8+ T cells are found in EBV-seropositive individuals than in EBV-seronegative controls at the baseline in the TN10 and AbATE trials. Mechanistically, single cell transcriptomics and functional assays identify the downregulation of NFκB and T cell activation pathways after treatment in EBV-seropositive patients; among diabetes antigen-specific CD8+ T cells, T cell receptor and mTOR signaling are also reduced. In parallel, signaling impairment is greater in adaptive than innate immune cells following teplizumab treatment in EBV-seropositive individuals. Our data thus indicate that EBV can impair signaling pathways in immune cells to modulate their responses in the context of type 1 diabetes.

Date: 2025
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-60276-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60276-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-60276-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().