Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 202, Issue 3, Pages 395-404Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20050117
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Funding
- NCI NIH HHS [R01 CA092123, CA92123] Funding Source: Medline
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Apoptosis-related genes play important roles in thymocyte maturation. We show that cellular FLICE-like inhibitory protein (c-FLIP), a procaspase-8-like apoptotic regulator, plays an essential role in the efficient development of mature T lymphocytes. Mice conditionally lacking c-FLIP in T lymphocytes display severe defects in the development of mature T cells, as indicated by a dramatically reduced number of CD4(+) and CD8(+) T cells in the spleen and lymph nodes of mutant mice. The impaired T lymphocyte maturation in c-FLIP conditional knockout mice occurs at the single-positive thymocyte stage and may be caused by enhanced apoptosis in vivo. Moreover, although c-FLIP has been implicated in T cell receptor signaling through nuclear factor (NF)-kappa B and Erk pathways, activation of NF-kappa B and Erk in c-FLIP-deficient thymocytes appears largely intact. Collectively, our data suggest that the primary role of c-FLIP in thymocyte maturation is to protect cells from apoptosis.
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