Publikation: Transforming growth factor β1 inhibits Fas ligand expression and subsequent activation-induced cell death in T cells via down-regulation of c-Myc
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Activation-induced cell death (AICD) is a process that regulates the size and the duration of the primary immune T cell response. In this report, we investigated the mechanisms involved in the regulation of AICD by transforming growth factor b1 (TGFb1). We found that TGFb1 decreased apoptosis of human T cells or T cell hybridomas after activation by anti-CD3. This decrease was associated with inhibition of Fas (Apo-1/CD95) ligand (FasL) expression, whereas Fas signaling was not affected by TGFb1. In parallel, TGFb1 inhibited c-Myc expression in T cell hybridomas, and ectopic expression of a chimeric molecule composed of c-Myc and the steroid binding domain of the estrogen receptor (Myc-ER) blocked both the inhibition of FasL and the decrease of AICD induced by TGFb1, providing that 4-hydroxytamoxifen was present. These results identify one mechanism by which TGFb1 blocks AICD to allow the clonal expansion of effector T cells and the generation of memory T cells during immune responses.
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GENESTIER, Laurent, Shailaja KASIBHATLA, Thomas BRUNNER, Douglas R. GREEN, 1999. Transforming growth factor β1 inhibits Fas ligand expression and subsequent activation-induced cell death in T cells via down-regulation of c-Myc. In: Journal of Experimental Medicine. 1999, 189(2), pp. 231-239. ISSN 0022-1007. Available under: doi: 10.1084/jem.189.2.231BibTex
@article{Genestier1999Trans-14303, year={1999}, doi={10.1084/jem.189.2.231}, title={Transforming growth factor β1 inhibits Fas ligand expression and subsequent activation-induced cell death in T cells via down-regulation of c-Myc}, number={2}, volume={189}, issn={0022-1007}, journal={Journal of Experimental Medicine}, pages={231--239}, author={Genestier, Laurent and Kasibhatla, Shailaja and Brunner, Thomas and Green, Douglas R.} }
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