Infective, neoplastic, and homeostatic sequelae of the loss of perforin function in humans

Abstract

Perforin, a pore-forming protein toxin synthesized and stored in the cytoplasmic vesicles of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells, is secreted when these effector lymphocytes encounter virus-infected or neoplastic cells. Perforin is encoded by a single-copy gene and is critical for immune homeostasis and defense of the organism against intracellular sepsis. A complete deficiency of perforin expression in either mice or humans is associated with a syndrome of immune insufficiency and severely deregulated lymphoid homeostasis. Humans who inherit inactivating mutations of perforin or defects in various parts of the cellular machinery that delivers perforin to the target ..