Lymphocyte-mediated cytolysis: dual apoptotic mechanisms with overlapping cytoplasmic and nuclear signalling pathways.

Abstract

Cytotoxic T lymphocytes (CTL) and natural killer (NK) cells together comprise cytotoxic lymphocytes (CL), which are the principal basis for the immune system’s detection and destruction of virus-infected or transformed cells. Although CTL and NK cells recognize foreign antigens and become activated in very different ways, both cell types employ the same two contact-dependent cytolytic mechanisms. In the first, the synergy of two granule-bound factors, a calcium-dependent pore-forming protein, perforin, and a collection of proteases (“granzymes”), results in the entry of effector proteases into the target cell cytoplasm and nucleus. The second mechanism involves trimerization of Fas (CD95/APO..