| First Author | Dohrman A | Year | 2005 |
| Journal | J Immunol | Volume | 175 |
| Issue | 1 | Pages | 311-8 |
| PubMed ID | 15972663 | Mgi Jnum | J:100574 |
| Mgi Id | MGI:3588894 | Doi | 10.4049/jimmunol.175.1.311 |
| Citation | Dohrman A, et al. (2005) Cellular FLIP long form augments caspase activity and death of T cells through heterodimerization with and activation of caspase-8. J Immunol 175(1):311-8 |
| abstractText | Caspase activity is required not only for the death of T cells, but also for their activation. A delicate balance of caspase activity is thus required during T cell activation at a level that will not drive cell death. How caspase activity is initiated and regulated during T cell activation is not known. One logical candidate for this process is cellular FLIP long form (c-FLIP(L)), because it can block caspase-8 recruitment after Fas (CD95) ligation as well as directly heterodimerize with and activate caspase-8. The current findings demonstrate that after T cell activation, caspase-8 and c-FLIP(L) associate in a complex enriched for active caspases. This occurs coincidently with the cleavage of two known caspase-8 substrates, c-FLIP(L) and receptor interacting protein 1. Caspase activity is higher in wild-type CD8(+) than CD4(+) effector T cells. Increased expression of c-FLIP(L) results in augmented caspase activity in resting and effector T cells to levels that provoke cell death, especially of the CD8 subset. c-FLIP(L) is thus not only an inhibitor of cell death by Fas, it can also act as a principal activator of caspases independently of Fas. |
