| First Author | Ma H | Year | 2020 |
| Journal | Cell Rep Med | Volume | 1 |
| Issue | 6 | Pages | 100097 |
| PubMed ID | 33205073 | Mgi Jnum | J:348114 |
| Mgi Id | MGI:7627241 | Doi | 10.1016/j.xcrm.2020.100097 |
| Citation | Ma H, et al. (2020) Human T Cells Expressing a CD19 CAR-T Receptor Provide Insights into Mechanisms of Human CD19-Positive beta Cell Destruction. Cell Rep Med 1(6):100097 |
| abstractText | Autoimmune destruction of pancreatic beta cells underlies type 1 diabetes (T1D). To understand T cell-mediated immune effects on human pancreatic beta cells, we combine beta cell-specific expression of a model antigen, CD19, and anti-CD19 chimeric antigen receptor T (CAR-T) cells. Coculturing CD19-expressing beta-like cells and CD19 CAR-T cells results in T cell-mediated beta-like cell death with release of activated T cell cytokines. Transcriptome analysis of beta-like cells and human islets treated with conditioned medium of the immune reaction identifies upregulation of immune reaction genes and the pyroptosis mediator GSDMD as well as its activator CASP4. Caspase-4-mediated cleaved GSDMD is detected in beta-like cells under inflammation and endoplasmic reticulum (ER) stress conditions. Among immune-regulatory genes, PDL1 is one of the most upregulated, and PDL1 overexpression partially protects human beta-like cells transplanted into mice. This experimental platform identifies potential mechanisms of beta cell destruction and may allow testing of therapeutic strategies. |
