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Participation of FLIP, RIP and Bcl‐x L in Fas‐mediated T‐cell Death
Author(s) -
Djerbi M.,
Malinowski M. M.,
Yagita H.,
Zhivotovsky B.,
Grandien A.
Publication year - 2007
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.2007.01957.x
Subject(s) - fas receptor , programmed cell death , haematopoiesis , apoptosis , cd8 , biology , flip , microbiology and biotechnology , autoimmunity , caspase 8 , cytotoxic t cell , t cell , cancer research , caspase , immunology , stem cell , immune system , genetics , in vitro
Apart from the conventional Fas signalling pathway, alternative pathways including the mitochondrial caspase‐dependent and RIP‐mediated cell death routes have been proposed to operate during Fas‐mediated cell death. To evaluate the contribution of different Fas signalling pathways, mice overexpressing FLIP L , Bcl‐x L , a kinase‐deficient form of RIP (RIPΔkin) or combinations thereof were generated by retroviral gene transfer of haematopoietic stem cells. Such mice did not show overt abnormalities in haematopoietic development, defects in thymic deletion, accumulation of double‐negative T cells or signs of autoimmunity. Fas‐mediated death of mitogen‐activated T cells was caspase dependent and could be blocked by FLIP L overexpression only with the minor involvement of Bcl‐x L or RIPΔkin inhibitable pathways. Fas‐mediated death of resting CD4 + and CD8 + T cells was mainly caspase dependent but could only partly be blocked by FLIP L overexpression. Both Bcl‐x L or RIPΔkin expression resulted in partial protection of CD8 + T cells against Fas‐mediated cell death. These results indicate that yet uncharacterized signalling pathways from the Fas receptor are critically involved in lymphoproliferative and autoimmune disease observed in lpr mice and autoimmune lymphoproliferative syndrome patients.