Normal thymocyte negative selection in TRAIL-deficient mice.
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.
Cretney
Erika
E
Cancer Immunology Program, Trescowthick Laboratories, Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett St., Melbourne, Victoria 8006, Australia.
Uldrich
Adam P
AP
Berzins
Stuart P
SP
Strasser
Andreas
A
Godfrey
Dale I
DI
Smyth
Mark J
MJ
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins; D017637:Clonal Deletion; D017353:Gene Deletion; D008198:Lymph Nodes / Q000166:cytology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology*; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D053221:TNF-Related Apoptosis-Inducing Ligand; C505654:Tnfsf10 protein, mouse; D014409:Tumor Necrosis Factor-alpha