Mechanisms of lymphocyte-mediated lysis

Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells use multiple mechanisms to destroy their target cells. Pore formation resulting in osmotic lysis of the target is one mechanism; the pore-forming protein (perforin) responsible for this activity has been purified. Antigenically and functionally it resembles proteins of the membrane attack complex of complement. The other known mediators of cytotoxicity appear to be closely interrelated. Tumor necrosis factor (TNF), lymphotoxin (LT), and leukalexin are the three members of this group that have been purified, although their mechanisms of action are still unknown. CTLs fragment the DNA of target cells, as do TNF, LT, and leukalexin; this may be one of the mechanisms of action of these mediators. CTLs and NK cells do not self lyse. The basis of this phenomenon is unclear, although recent advances have shed some light on the problem.