The major defense of the body against virus-infected and tumorigenic cells is cytotoxic T lymphocyte (CTL)-mediated cytotoxicity, which also plays a role in autoimmune diseases and transplant rejection. During CTL-mediated cytotoxicity, CTL granules containing perforin are exocytosed. Perforin is a pore-forming protein that facilitates the entry of cytotoxic serine proteases, such as granzymes, into target cells by forming transmembrane channels in target cell membranes. Perforin is primarily expressed in cytotoxic T lymphocytes (CTL) and natural killer (NK) cells, but has also been observed in an astrocyte population of the human brain. It has been shown that abrogation of perforin function by Ca2+-complexing agents leads to decreased levels of necrosis, demonstrating that both necrosis and apoptosis contribute to CTL-mediated cytotoxicity. Perforin activity has been shown to be induced by IL-2, IL-3, IL-4, IL-6 and to a lesser degree, TNF and IFN-_.
