Abstract
Mechanistically T-cell mediated cytotoxicity uses two pathways for the destruction of a target cell. One is directed at the target membrane and the other at the target nucleus and DNA. These pathways often operate together and at least partially overlap by their common usage of perforin. Perforin mediates direct target membrane damage by pore formation and subverting the normal barrier function of the membrane. This action alone often is sufficient for target cell death. In addition perforin pores allow the entry of other molecules into the target cell either by diffusion across the pore or by uptake through repair endocytosis. Entry of Ca ions, of TNF and/or of granzymes by these mechanism may trigger apoptosis of the target cell. The membrane permeabilizing action of perforin thus also appears to be a requisite for apoptosis which is triggered by the entry of Ca and/or other factors.