TRAILing autoimmune disease

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF family that selectively induces apoptosis of tumor cells, but its role in normal cells remains unclear. In the February 10 Nature Immunology, Sally-Eddine Lamhamedi-Cherradi and colleagues at the School of Medicine, University of Pennsylvania, USA, show that in mice TRAIL mediates thymocyte apoptosis and is important in the induction of autoimmune diseases (Nature Immunology, DOI:10.1038/ni894, February 10, 2003).

Lamhamedi-Cherradi et al. used TRAIL^+/+ and TRAIL^–/– C57BL/6 mice immunized with chicken type II collagen. They observed that mice deficient in TRAIL had a severe defect in thymocyte apoptosis, and thymic deletion induced by T cell receptor ligation was severely impaired. In addition, they showed that TRAIL^–/– mice were hypersensitive to collagen-induced arthritis and streptozotocin-induced diabetes and developed autoimmune responses.

"The results reported here indicate that TRAIL-deficient mice not only have a defect in negative selection, but also have ...