Normal thymocyte negative selection in TRAIL-deficient mice.

Erika Cretney; Adam P Uldrich; Stuart P Berzins; Andreas Strasser; Dale I Godfrey; Mark J Smyth

doi:10.1084/jem.20030634

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PubMed · 12900523

Normal thymocyte negative selection in TRAIL-deficient mice.

Erika Cretney·Adam P Uldrich·Stuart P Berzins·Andreas Strasser·Dale I Godfrey·Mark J Smyth

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Abstract

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.

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Animals Antigens, CD Apoptosis Regulatory Proteins Clonal Deletion Gene Deletion Lymph Nodes Membrane Glycoproteins Mice Mice, Inbred BALB C Mice, Inbred C57BL Receptor-CD3 Complex, Antigen, T-Cell Signal Transduction Spleen T-Lymphocyte Subsets T-Lymphocytes TNF-Related Apoptosis-Inducing Ligand Tumor Necrosis Factor-alpha Journal Article Research Support, Non-U.S. Gov't

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Erika Cretney, Adam P Uldrich, Stuart P Berzins, Andreas Strasser, Dale I Godfrey, Mark J Smyth. 2003-08-04. Normal thymocyte negative selection in TRAIL-deficient mice.. https://doi.org/10.1084/jem.20030634

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