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TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) is a recently identified member of the tumor necrosis factor cytokine superfamily. TRAIL has been shown to induce apoptosis in various tumor cell lines, whereas most primary cells seem to be resistant. These observations have raised considerable interest in the use of TRAIL in tumor therapy. Yet little is known about the physiological function of TRAIL. This is particularly the case in the immune system, where TRAIL has been suggested by some to be involved in target cell killing and lymphocyte death. We have developed a panel of mAbs and soluble proteins to address the role of TRAIL in lymphocyte development. These studies demonstrate activation-induced sensitization of thymocytes to TRAIL-mediated apoptosis and expression of the apoptosis-inducing TRAIL receptors. However, with the use of several model systems, our subsequent experiments rule out the possibility that TRAIL plays a major role in antigen-induced deletion of thymocytes. In contrast to thymocytes, there is no up-regulation of TRAIL receptors in peripheral T cells on activation, which remain resistant to TRAIL. Thus, susceptibility to TRAIL-induced apoptosis is controlled differently by central and peripheral T cells.

Original publication

DOI

10.1073/pnas.091100398

Type

Journal article

Journal

Proc Natl Acad Sci U S A

Publication Date

24/04/2001

Volume

98

Pages

5158 - 5163

Keywords

ATP-Binding Cassette Transporters, Animals, Antibodies, Monoclonal, Antigen Peptide Transporter-1, Antigens, CD4, Antigens, CD8, Apoptosis, Apoptosis Regulatory Proteins, Cells, Cultured, Child, Preschool, Clonal Deletion, Cytotoxicity, Immunologic, Flow Cytometry, Genes, RAG-1, Humans, Infant, Jurkat Cells, Lymphocyte Activation, Membrane Glycoproteins, Mice, Mice, Knockout, Organ Culture Techniques, Receptors, TNF-Related Apoptosis-Inducing Ligand, Receptors, Tumor Necrosis Factor, T-Lymphocytes, TNF-Related Apoptosis-Inducing Ligand, Thymus Gland, Tumor Necrosis Factor-alpha