T cell lysis of murine renal cancer: multiple signaling pathways for cell death via Fas

Activated T cells lyse the murine renal cancer Renca. We have examined the mechanism of tumor cell lysis with the use of T tells derived from C57BL/6, BALB/c, B6.gld, and B6.Pfp(-/-) mice, C57BL/6 and BALB/c T cells can lyse Renca cells through the use of both granule- and Fas Ligand (FasL)-mediated pathways. However, B6.gld T cells predominantly use granule-mediated killing, whereas B6.Pfp(-/-) T cells use Fast. The lysis of Renca by Pfp(-/-) T cells is only partially inhibited by the caspase inhibitor ZVAD-FMK, suggesting that caspase-independent signaling is also important for Renca cell lysis, When the reactive oxygen scavenger butylated hydroxyanisole was used alone or hi combination with ZVAD-FMK a substantial reduction of Renca lysis was observed. Therefore, the caspase-independent generation of reactive oxygen intermediates in Renca after Fas triggering contributes to the lysis of these cells.