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

T. J. Sayers, A. D. Brooks, N. Seki, M. J. Smyth, H. Yagita, B. R. Blazar, A. M. Malyguine

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)81-86
Number of pages6
JournalJournal of Leukocyte Biology
Volume68
Issue number1
StatePublished - 2000

Keywords

  • Cell-mediated cytotoxicity
  • Fas ligand
  • Kidney cancer
  • Renca cells

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