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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 

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Cellular FLICE-inhibitory protein is required for T cell survival and cycling.

Fas-associated death domain (FADD) and caspase-8 are key signal transducers for death receptor-induced apoptosis, whereas cellular FLICE-inhibitory protein (cFLIP) antagonizes this process. Interestingly, FADD and caspase-8 also play a role in T cell development and T cell receptor (TCR)-mediated proliferative responses. To investigate the underlying mechanism, we generated cFLIP-deficient T cells by reconstituting Rag-/- blastocysts with cFLIP-deficient embryonic stem cells. These Rag chimeric mutant mice (rcFLIP-/-) had severely reduced numbers of T cells in the thymus, lymph nodes, and spleen, although mature T lymphocytes did develop. Similar to FADD- or caspase-8-deficient cells, rcFLIP-/- T cells were impaired in proliferation in response to TCR stimulation. Further investigation revealed that cFLIP is required for T cell survival, as well as T cell cycling in response to TCR stimulation. Interestingly, some signaling pathways from the TCR complex appeared competent, as CD3 plus CD28 cross- linking was capable of activating the ERK pathway in rcFLIP-/- T cells. We demonstrate an essential role for cFLIP in T cell function.[1]

References

  1. Cellular FLICE-inhibitory protein is required for T cell survival and cycling. Chau, H., Wong, V., Chen, N.J., Huang, H.L., Lin, W.J., Mirtsos, C., Elford, A.R., Bonnard, M., Wakeham, A., You-Ten, A.I., Lemmers, B., Salmena, L., Pellegrini, M., Hakem, R., Mak, T.W., Ohashi, P., Yeh, W.C. J. Exp. Med. (2005) [Pubmed]
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