Activated T cell death in vivo mediated by proapoptotic bcl-2 family member bim.

By David A Hildeman, Yanan Zhu, T. Mitchell, P. Bouillet, A. Strasser, J. Kappler, P. Marrack. Immunity, 2002

655 citations recorded by the source corpus.

At the end of the T cell response, the majority of the activated T cells die. We activated Vbeta8(+) T cells with staphylococcal enterotoxin B (SEB) in vivo and monitored the expansion and deletion of Vbeta8(+) T cells. We found that, in response to SEB, activated T cells died in vivo in the absence of Fas or TNF-R signaling but not when they overexpressed human Bcl-2. We also found that Vbeta8(+) T cells from Bim-deficient mice are resistant to SEB-induced deletion. While Bim levels did not change, endogenous Bcl-2 levels within Vbeta8(+) T cells decrease following SEB injection. Thus, the death of superantigen-stimulated T cells in vivo is mediated by Bim and may be modulated by a decrease in Bcl-2.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/adf9cb43d6daa67decd065034193bbddb275801d

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In Immunology

1. S. Nagata
2. P. Jost
3. A. Strasser
4. Jerry M. Adams
5. Suzanne Cory
6. Inna N. Lavrik
7. A. Abbas
8. P. Krammer

Citations in the corpus

• Life and death in peripheral T cells (2007, background): “The pro-apoptotic BCL-2 family member BIM (BCL-2-interacting mediator of cell death; also known as BCL2L11) is essential for ACAD, and BIM and its family member PUMA (p53-upregulated modulator of apoptosis; also known as BBC3) mediate cell death in T cells by the intrinsic apoptotic pathwa”
• The Bcl-2 apoptotic switch in cancer development and therapy (2007, background): “Bim is also critical for shaping the immune repertoire by eliminating thymocytes that recognize self-antigens (Bouillet et al., 2002) and in terminating T-cell immune responses (Hildeman et al., 2002; Pellegrini et al., 2003).”
• Activation‐induced cell death in T cells (2003, background): “As with negative selection, the activation and function of Bim has been implicated in peripheral deletion (59, 60).”
• The many roles of FAS receptor signaling in the immune system (2009, positive): “Indeed, the first clear demonstration for a role of FAS-induced apoptosis in the shut-down of a T cell immune response came from studies in which mice were repeatedly injected with SEB (Strasser et al., 1995), thereby mimicking a chronic infection.”
• The Bcl-2 family: roles in cell survival and oncogenesis (2003, background): “For example, Bim is required for deletion of autoreactive lymphocytes in vivo (Bouillet et al., 2002; Hildeman et al., 2002) and for apoptosis of T cells in vitro following cytokine deprivation, calcium flux or treatment with Taxol (paclitaxel) but not markedly for apoptosis induced by…”
• Interferon γ is required for activation-induced death of T lymphocytes (2002, background): “This type of stimulation results in activation of pro-apoptotic members of the bcl-2 family, such as Bim, in the absence of antiapoptotic members, and T cell death without engagement of death receptors ( 13 ).”
• ER stress triggers apoptosis by activating BH3-only protein Bim. (2007, background): “, 2003) and shutdown of T cell immune responses (Hildeman et al., 2002).”