Normal thymocyte negative selection in TRAIL-deficient mice

• Published in: The Journal of experimental medicine Vol. 198; no. 3; pp. 491 - 496
• Main Authors: Cretney, Erika, Uldrich, Adam P, Berzins, Stuart P, Strasser, Andreas, Godfrey, Dale I, Smyth, Mark J
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 04.08.2003
• Subjects: Animals; Antigens, CD - metabolism; Apoptosis Regulatory Proteins; Brief Definitive Report; Clonal Deletion; Gene Deletion; Lymph Nodes - cytology; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Receptor-CD3 Complex, Antigen, T-Cell - metabolism; Signal Transduction - physiology; Spleen - cytology; T-Lymphocyte Subsets; T-Lymphocytes - cytology; T-Lymphocytes - physiology; TNF-Related Apoptosis-Inducing Ligand; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.20030634

The molecular basis of thymocyte negative selection, which plays a critical role in establishing and maintaining immunological tolerance, is not yet resolved. In particular, the importance of the death receptor subgroup of the tumor necrosis factor (TNF)-family has been the subject of many investigations, with equivocal results. A recent report suggested that TRAIL was a critical factor in this process, a result that does not fit well with previous studies that excluded a role for the FADD-caspase 8 pathway, which is essential for TRAIL and Fas ligand (FasL) signaling, in negative selection. We have investigated intrathymic negative selection of TRAIL-deficient thymocytes, using four well-established models, including antibody-mediated TCR/CD3 ligation in vitro, stimulation with endogenous superantigen in vitro and in vivo, and treatment with exogenous superantigen in vitro. We were unable to demonstrate a role for TRAIL signaling in any of these models, suggesting that this pathway is not a critical factor for thymocyte negative selection.