The Journal of Experimental Medicine
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Published 4 August 2003. doi:10.1084/jem.20030634
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© Rockefeller University Press, 0022-1007/2003/8/491 $5.00
The Journal of Experimental Medicine, Volume 198, Number 3, 491-496

Brief Definitive Report

 Normal Thymocyte Negative Selection in TRAIL-deficient Mice

Erika Cretney1, Adam P. Uldrich2, Stuart P. Berzins2, Andreas Strasser3, Dale I. Godfrey2 and Mark J. Smyth1

1 Cancer Immunology Program, Trescowthick Laboratories, Peter MacCallum Cancer Centre, Melbourne, Victoria 8006, Australia
2 Department of Pathology and Immunology, Monash University Medical School, Prahran 3181, Australia
3 The Walter and Eliza Hall Institute of Medical Research, Royal Pde, Parkville 3050, Australia

Address correspondence to M.J. Smyth, Cancer Immunology Program, Trescowthick Laboratories, Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett St., Melbourne, Victoria 8006, Australia. Phone: 61-3-9656-3728; Fax: 61-3-9656-1411; email: m.smyth{at}pmci.unimelb.edu.au

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.

Key Words: T cell selection • thymus • apoptosis • tumor necrosis factor • antigen


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