* Intramural Research Support Program,
¶ Clinical Services Program, SAIC-Frederick,
Laboratory of Experimental Immunology, DBS, NCI-FCRDC, Frederick, Maryland;
Cellular Cytotoxicity Laboratory, The Austin Research Institute, Heidelberg, Victoria, Australia;
Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan; and
|| Department of Pediatrics, Division of Bone Marrow Transplantation, University of Minnesota, Minneapolis
Correspondence: Dr. Thomas Sayers, SAIC-Frederick, NCI-FCRDC, Building 560, Room 31-30, Frederick, MD 21702-1201. E-mail: Sayers{at}mail.ncifcrf.gov
Activated T cells lyse the murine renal cancer Renca. We have examined the mechanism of tumor cell lysis with the use of T cells 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 FasL. 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 in 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.
Key Words: Fas ligand • cell-mediated cytotoxicity • Renca cells • kidney cancer
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