Beta cell extracellular vesicle PD‑L1 as a novel regulator of CD8 +T cell activity and biomarker during the evolution of type 1 diabetes – published online 07/11/2024

Chaitra Rao, Daniel T. Cater, Saptarshi Roy, Jerry Xu, Andre G. De Oliveira, Carmella Evans‑Molina, Jon D. Piganelli, Decio L. Eizirik, Raghavendra G. Mirmira, Emily K. Sims

Beta cell extracellular vesicle (EV) cargo differs under conditions of health and disease and may mediate extracellular interactions within the islet microenvironment. In this issue, Rao, Cater et al (https://doi.org/10.1007/s00125-024-06313-2) demonstrate that the immune checkpoint protein programmed death-ligand 1 (PD-L1) is present on the beta cell EV surface and upregulated by exposure of islets to IFN. The authors found that beta cell EV PD-L1 was able to bind PD-1 in a dose-dependent manner, and that treatment of activated CD8⁺ T cells with beta cell EV PD-L1 reduced T cell proliferation and cytokine production. They also report that plasma EV PD-L1 was increased in islet autoantibody-positive individuals, especially in those who had single autoantibody positivity, as compared with an islet autoantibody-negative control group. Moreover, in both autoantibody-positive individuals, in early disease stages, and in individuals with recently diagnosed stage 3 type 1 diabetes, plasma EV PD-L1 positively correlated with plasma C-peptide. The authors conclude that these findings support a potential link between higher EV PD-L1 and beta cell survival and suggest that EV PD-L1 could be exploited as a means to inhibit immune-mediated beta cell death.