Cell-mediated killing: effector mechanisms and mediators

Cytolytic T lymphocytes and natural killer cells appear to mediate cell killing by several different mechanisms. In one mechanism, a pore-forming protein, called perforin or cytolysin, is exocytosed by the effector cell and is inserted into the plasma membrane of the target cells, thereby collapsing its permeability barrier. Alternatively, the cytolytic cells activate a pathway of programmed cell death that causes specific fragmentation of target cell DNA. The physiological circumstances that determine which mechanism will be employed by the effector cells have not yet been fully determined. Recent experiments suggest that perforin is employed in situations in which there are high local concentrations of interleukin-2, such as cancer and acute viral infections, while a role for the programmed cell death pathway remains to be elucidated.