Killing of Human β-Cells by CD8+ T Cells Triggers Inflammatory Paracrine Signaling and Neighboring β-Cell Dysfunction
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.
Authors
- Masaya Oshima (ORCID: https://orcid.org/0000-0002-9774-0931)
- Raphaël Scharfmann (ORCID: https://orcid.org/0000-0001-7619-337X)
- Alexis Fouque
- Barbara Brandao (ORCID: https://orcid.org/0009-0008-0128-0100)
- Clémentine Halliez (ORCID: https://orcid.org/0000-0002-5683-515X)
- Roberto Mallone (ORCID: https://orcid.org/0000-0002-9846-8861)
- Diego Balboa (ORCID: https://orcid.org/0000-0002-4784-5452)
- Farah Kobaisi (ORCID: https://orcid.org/0000-0001-9193-1588)
- Otto Mayer (ORCID: https://orcid.org/0000-0002-8023-3749)
- Nina Modé
Institutions
- Université Paris-Panthéon-Assas (FR)
- University of Helsinki (FI)
- Inserm (FR)
- Université Paris Cité (FR)
- Indiana Biosciences Research Institute (US)
- Hôpital Cochin (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Institute for Molecular Medicine Finland (FI)
- Institut Cochin (FR)
Publication Details
- Journal
- Diabetes
- Published
- 2025-11-11
- DOI
- https://doi.org/10.2337/db25-0473
- Primary Topic
- Diabetes and associated disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.00