| First Author | Salmena L | Year | 2003 |
| Journal | Genes Dev | Volume | 17 |
| Issue | 7 | Pages | 883-95 |
| PubMed ID | 12654726 | Mgi Jnum | J:82759 |
| Mgi Id | MGI:2655005 | Doi | 10.1101/gad.1063703 |
| Citation | Salmena L, et al. (2003) Essential role for caspase 8 in T-cell homeostasis and T-cell-mediated immunity. Genes Dev 17(7):883-95 |
| abstractText | Defects in death receptor-mediated apoptosis have been linked to cancer and autoimmune disease in humans. The in vivo role of caspase 8, a component of this pathway, has eluded analysis in postnatal tissues because of the lack of an appropriate animal model. Targeted disruption of caspase 8 is lethal in utero. We generated mice with a targeted caspase 8 mutation that is restricted to the T-cell lineage. Despite normal thymocyte development in the absence of caspase 8, we observed a marked decrease in the number of peripheral T-cells and impaired T-cell response ex vivo to activation stimuli. caspase 8 ablation protected thymocytes and activated T-cells from CD95 ligand but not anti-CD3-induced apoptosis, or apoptosis activated by agents that are known to act through the mitochondria. caspase 8 mutant mice were unable to mount an immune response to viral infection, indicating that caspase 8 deletion in T-cells leads to immunodeficiency. These findings identify an essential, cell-stage-specific role for caspase 8 in T-cell homeostasis and T-cell-mediated immunity. This is consistent with the recent identification of caspase 8 mutations in human immunodeficiency. |
