Anti-CD3 mAb treatment reshapes infiltrating T and β cells in the islets in autoimmune diabetes
Ying Wu, Maxwell Spurrell, Ana Lledó-Delgado, Songyan Deng, Dejiang Wang, Yang Liu, Mahsa Nouri Barkestani, Ana Luisa Perdigoto, Kevan C. Herold
TL;DR
Anti-CD3 monoclonal antibody treatment reshapes immune cells in the pancreas, leading to temporary tolerance in type 1 diabetes.
Contribution
The study reveals how anti-CD3 mAb treatment alters T and β cells in islets to induce operational tolerance in diabetes.
Findings
T cells in islets become more heterogeneous with hybrid features after anti-CD3 mAb treatment.
Autoantigen-reactive CD8+ T cells persist but show reduced pathogenicity and stem-like traits.
β cells and T cells are reshaped to create a tenuous state of operational tolerance.
Abstract
Treatment with anti-CD3 monoclonal antibody (mAb) can delay or prevent type 1 diabetes in mice and humans by modulating the immune-mediated destruction of β cells. A single course of treatment may have lasting efficacy, but the mechanisms that account for these prolonged effects, i.e., “operational tolerance,” are not clear. Here, we used paired single-cell RNA and T cell receptor sequencing to characterize islet-infiltrating T cells and their counterpart in paired pancreatic lymph nodes from anti-CD3 mAb–treated nonobese diabetic (NOD) mice in remission. We found that after anti-CD3 mAb treatment, T cells that infiltrate the islets are more heterogeneous and have hybrid features including characteristics of T stem cell–like memory and reduced effector function compared with those from untreated prediabetic NOD mice. Autoantigen-reactive CD8+ T cells persist after treatment, but they…
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Taxonomy
TopicsDiabetes and associated disorders · Pancreatic function and diabetes · T-cell and B-cell Immunology