ArticleCell death and differentiation2012
Elevated Mcl-1 inhibits thymocyte apoptosis and alters thymic selection.
Article in Cell death and differentiation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- The broad impact of cell death genes on the human disease phenome.Cell death & disease · 2024Article
- Association of T cell infiltration and morphological change of thymus gland with the aggravation of pulmonary emphysema in testosterone deficiency.Biochemistry and biophysics reports · 2023Article
- The Adaptation Model of Immunity: Signal IV Matters Most in Determining the Functional Outcomes of Immune Responses.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- The multiple mechanisms of MCL1 in the regulation of cell fate.Communications biology · 2021Review
- Impact of elevated anti-apoptotic MCL-1 and BCL-2 on the development and treatment of MLL-AF9 AML in mice.Cell death and differentiation · 2019Article
- PTPN2 regulates T cell lineage commitment and αβ versus γδ specification.The Journal of experimental medicine · 2017Article
- Life and Death of Activated T Cells: How Are They Different from Naïve T Cells?Frontiers in immunology · 2017Review
- Re-activation of mitochondrial apoptosis inhibits T-cell lymphoma survival and treatment resistance.Leukemia · 2016Article
- Loss of Bak enhances lymphocytosis but does not ameliorate thrombocytopaenia in BCL-2 transgenic mice.Cell death and differentiation · 2014Article
- Getting away with murder: how does the BCL-2 family of proteins kill with immunity?Annals of the New York Academy of Sciences · 2013Review
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
T cells developing in the thymus undergo rigorous positive and negative selection to ensure that those exported to peripheral lymphoid organs bear T-cell receptors (TCRs) capable of reacting with foreign antigens but tolerant of self. At each checkpoint, whether a thymocyte survives or dies is determined by antiapoptotic and proapoptotic Bcl-2 family members. We used Mcl-1 transgenic (tg) mice to investigate the impact of elevated expression of antiapoptotic Mcl-1 on thymocyte apoptosis and selection, making a side-by-side comparison with thymocytes from BCL-2tg mice. Mcl-1 was as effective as Bcl-2 at protecting thymocytes against spontaneous cell death, diverse cytotoxic insults and TCR-CD3 stimulation-driven apoptosis. In three different TCR tg models, Mcl-1 markedly enhanced positive selection of thymocytes, as did Bcl-2. In H-Y TCR tg mice, elevated Mcl-1 and Bcl-2 were equally effective at inhibiting deletion of autoreactive thymocytes. However, in the OT-1tg model where deletion is mediated by a peripheral antigen whose expression is regulated by Aire, Mcl-1 was less effective than Bcl-2. Thus, the capacity of Mcl-1 overexpression to inhibit apoptosis triggered by TCR stimulation apparently depends on the thymocyte subset subject to deletion, presumably due to differences in the profiles of proapoptotic Bcl-2 family members mediating the deletion.
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