Caspase enzyme activity is not essential for apoptosis during thymocyte development
In: Journal of immunology (Baltimore, Md. : 1950), Jg. 164 (2001-02-07), Heft 8
Online
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Zugriff:
Caspases, a family of cysteine proteases, are critical mediators of apoptosis. To address the importance of caspases in thymocyte development, we have generated transgenic mice that express the baculovirus protein p35, a viral caspase inhibitor, specifically in the thymus. p35 expression inhibited Fas (CD95)-, CD3-, or peptide-induced caspase activity in vitro and conferred resistance to Fas-induced apoptosis. However, p35 did not block specific peptide-induced negative selection in OT1 and HY TCR transgenic mouse models. Even the potent pharmacological caspase inhibitor zVAD-FMK (benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl-ketone) could not prevent peptide-induced deletion of OT1 thymocytes, although it improved basal thymocyte survival in vitro. Moreover, the developmental block observed in rag1−/− thymocytes, which lack pre-TCR signaling, was also not rescued by p35 expression. These results indicate that caspase-independent signal transduction pathways can mediate thymocyte death during normal T cell development.
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Caspase enzyme activity is not essential for apoptosis during thymocyte development
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Autor/in / Beteiligte Person: | Doerfler, Petra ; Perlmutter, Roger M. ; Forbush, Katherine A. |
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Zeitschrift: | Journal of immunology (Baltimore, Md. : 1950), Jg. 164 (2001-02-07), Heft 8 |
Veröffentlichung: | 2001 |
Medientyp: | unknown |
ISSN: | 0022-1767 (print) |
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