Two distinct pathways of specific killing revealed by perforin mutant cytotoxic T lymphocytes

Immunity. 1994 Aug;1(5):357-64. doi: 10.1016/1074-7613(94)90066-3.


To study the contribution of putative perforin-independent mechanism in the antigen-specific target destruction by cytotoxic T lymphocytes CD8+ CTL lines were established from spleen cells of chimeric mice produced by injecting perforin (-/-) embryonic stem cells into blastocysts of RAG-2(-/-) mice. When tested on normal concanavalin A blasts, these perforin-deficient cytotoxic T lymphocyte lines were found to be capable of inducing antigen-specific target cell lysis accompanied by DNA degradation. In contrast, with target cells carrying a mutation in Fas molecule, perforin-independent cytotoxicity was not detectable. These data not only confirmed the primary role of perforin but simultaneously revealed a major contribution of a perforin-independent Fas-mediated pathway in antigen-specific cytolysis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, Surface / pharmacology
  • Cell Death / drug effects
  • Cytotoxicity, Immunologic / drug effects
  • Humans
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / pharmacology
  • Mice
  • Mice, Inbred DBA
  • Mutation
  • Perforin
  • Pore Forming Cytotoxic Proteins
  • T-Lymphocytes, Cytotoxic / cytology*
  • T-Lymphocytes, Cytotoxic / physiology
  • fas Receptor


  • Antigens, Surface
  • Membrane Glycoproteins
  • Pore Forming Cytotoxic Proteins
  • fas Receptor
  • Perforin