Teplizumab induces persistent changes in the antigen-specific repertoire in individuals at risk for type 1 diabetes.

ABSTRACT: BACKGROUNDTeplizumab, a non-FcR-binding anti-CD3 mAb, is approved to delay progression of type 1 diabetes (T1D) in at-risk patients. Previous investigations described the immediate effects of the 14-day treatment, but longer-term effects of the drug remain unknown.METHODSWith an extended analysis of study participants, we found that 36% were undiagnosed or remained free of clinical diabetes after 5 years, suggesting operational tolerance. Using single-cell RNA sequencing, we compared the phenotypes, transcriptome, and repertoire of peripheral blood CD8+ T cells including autoreactive T cells from study participants before and after teplizumab and features of responders and non-responders.RESULTSAt 3 months, there were transcriptional signatures of cell activation in CD4+ and CD8+ T cells i

SUBMITTER: Lledo-Delgado A 

PROVIDER: S-EPMC11405034 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature