Oehme, Ina;
Neumann, Frank;
Bösser, Susanne;
Zörnig, Martin
Transgenic overexpression of the Caspase‐8 inhibitor FLIPshort leads to impaired T cell proliferation and an increased memory T cell pool after staphylococcal enterotoxin B injection
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Media type:
E-Article
Title:
Transgenic overexpression of the Caspase‐8 inhibitor FLIPshort leads to impaired T cell proliferation and an increased memory T cell pool after staphylococcal enterotoxin B injection
Contributor:
Oehme, Ina;
Neumann, Frank;
Bösser, Susanne;
Zörnig, Martin
Published:
Wiley, 2005
Published in:
European Journal of Immunology, 35 (2005) 4, Seite 1240-1249
Language:
English
DOI:
10.1002/eji.200425564
ISSN:
0014-2980;
1521-4141
Origination:
Footnote:
Description:
AbstractThe cellular homologues of the viral anti‐apoptotic v‐FLIP proteins exist as a long (c‐FLIPL) and a short (c‐FLIPS) splice variant. While c‐FLIPS and v‐FLIP are composed solely of two death effector domains, c‐FLIPL contains an (inactive) caspase‐like domain in addition to these two death effector domains, thereby structurally resembling pro‐Caspase‐8. Both c‐FLIPL and c‐FLIPS suppress apoptosis by inhibiting Caspase‐8 activation, although at different levels of pro‐Caspase‐8 processing. To analyze the consequences of deregulated c‐FLIPS expression in vivo, we established lck FLIPS‐transgenic mice overexpressing the transgene in thymocytes and in mature T cells. As expected, CD95L‐induced apoptosis was impaired in lck FLIPS‐transgenic T cells, indicating the functionality of the FLIPS transgene. Remarkably, activation‐induced cell death of transgenic T cells was unaffected, despite the observed inhibition of CD95‐induced T cell death. Thymic and splenic cell numbers as well as CD4/CD8 cellularity were normal in lck FLIPS‐transgenic animals, which in contrast to CD95‐deficient mice do not accumulate Thy1+ B220+ CD4– CD8– peripheral T cells. c‐FLIPS overexpression leads to a significant decrease in activation‐induced T cell proliferation in vitro. Despite the capacity of FLIPS to inhibit CD95‐induced apoptosis, T cell lymphomagenesis is not observed in lck FLIPS‐transgenic mice. Interestingly, the Vβ8+ memory T cell pool is enlarged upon staphylococcal enterotoxin B injections, suggesting a specific in vivo function for FLIPS in the maintenance of restimulated T cells.