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https://doi.org/10.1073/pnas.0400005101
Title: | Regulation of expression of Bcl-2 protein family member Bim by T cell receptor triggering | Authors: | Sandalova, Elena Wei, Cheng-Hong Masucci, Maria G Levitsky, Victor |
Issue Date: | 2-Mar-2004 | Publisher: | Proceedings of the National Academy of Sciences | Citation: | Sandalova, Elena, Wei, Cheng-Hong, Masucci, Maria G, Levitsky, Victor (2004-03-02). Regulation of expression of Bcl-2 protein family member Bim by T cell receptor triggering. Proceedings of the National Academy of Sciences 101 (9) : 3011-3016. ScholarBank@NUS Repository. https://doi.org/10.1073/pnas.0400005101 | Abstract: | Bim, a proapoptotic BH3-only member of the Bcl-2 protein family, is required for central and peripheral deletion of T lymphocytes. Mechanisms regulating Bim activity in T cells remain poorly understood. We show that expression of Bim is up-regulated in human T cells after polyclonal or specific T cell receptor triggering. Induction of Bim was affected by the agonistic potency of MHC:peptide ligands. Peptides that failed to induce Bim expression, failed to induce apoptosis in specific T cells, whereas partially agonistic ligands, which trigger death receptor-independent activation-induced cell death (AICD), induced Bim, but were inefficient in up-regulating Bcl-XL. Activation of protein kinase C and calcineurin appeared to be necessary and sufficient for Bim upregulation after T cell receptor ligation. Immunosuppressive drugs known to prevent T cell deletion in vivo, such as cyclosporin A or FK506, blocked Bim up-regulation and rescued T cells from death receptor-independent AICD, whereas rapamycin, which allows the development of stable immunological tolerance, did not exhibit these activities. These results define a new mode of Bim regulation, strongly implicate Bim as a mediator of AICD, and suggest that Bim up-regulation can be targeted to influence the outcome of specific immune responses. | Source Title: | Proceedings of the National Academy of Sciences | URI: | https://scholarbank.nus.edu.sg/handle/10635/226858 | ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.0400005101 |
Appears in Collections: | Staff Publications Elements |
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