Lymphocyte life and death: the caspase-8 connection.

Caspase-8 plays an important role in death receptor-mediated apoptosis. In contrast to its apoptotic function, recent studies have suggested caspase-8 also plays a role in the immune response, as caspase-8 is essential for lymphocyte proliferation in response to antigen stimulation. In the March 2005 issue of Science (2005; 307:1465-8), Su et al. provide compelling evidence supporting a role for caspase-8 in antigen receptor-induced NF-kappaB activation. They identified caspase-8 as an essential component in the activation of the IKK complex, linking IKK to the upstream Bcl10-MALT1 complex. Intriguingly, they demonstrated that it is not only the physical presence of caspase-8, but rather enzymatic activity that is required for the activation of NF-kappaB.