Molecular mechanisms of cytolysis induced by human lymphokine-activated killer cells

It has been shown that lysis of tumor target cells caused by lymphokine-act ivated killers is possible both upon a direct contact and in the presence o f isolated nongranular cytotoxic proteins. The contact of cytolytic lymphoc ytes with K-562 cells leads to Fas L activation on the lymphocyte membrane and secretion of a broad spectrum of soluble cytotoxic proteins immunologic ally related to Tag 7 described earlier. These proteins can form inactive c omplexes, which are reactivated upon heating and addition of ATP. The prote ins induced discrete cytolytic processes in tumor cells, differing in the r ate of cytolysis and the mechanism of the apoptotic signal transduction. Fa st processes (revealed in 3 h) mediated by caspases, and slow ones (in 24 h ) with the supposed involvement of mitochondria were detected. A scheme for the lymphokine-activated killer interaction with target tumor cells is pro posed.