Killing of Human β-Cells by CD8+ T Cells Triggers Inflammatory Paracrine Signaling and Neighboring β-Cell Dysfunction.

ARTICLE HIGHLIGHTS In type 1 diabetes, CD8+ T cells destroy pancreatic β-cells. Since most β-cells avoid direct T-cell contact, we asked whether bystander effects drive their dysfunction and loss. We asked whether CD8+ T cells can damage β-cells indirectly via bystander inflammation. By developing and using a chimeric pseudoislet model, we show that β-cell killing requires direct CD8+ T-cell contact, contact-free β-cells are impacted by inflammation, that these effects are reproduced using conditioned medium from activated CD8+ T cells, and that insulin secretion is preserved with reduced storage and impaired protein translation. Our model provides a platform to dissect type 1 diabetes pathogenesis and test therapies to preserve β cells.

• Publication year

  2025

• Venue

  Diabetes

• Publication date

  2025-11-11

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.2337/db25-0473PMID 41218919
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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