Fratricide of CD8+ cytotoxic T lymphocytes is dependent on cellular activation and perforin-mediated killing

Michael Wei Chih Su, Saiju Pyarajan, Jin Hong Chang, Chao Lan Yu, Yong Jiu Jin, York Dieter Stierhof, Peter Walden, Steven J. Burakoff

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


CD8+ CTL mediate the destruction of cells displaying foreign peptides in association with class I MHC molecules. Since CD8+ CTL themselves express class I MHC molecules, a phenomenon known as "fratricide" can be elicited by T cells presenting antigens to other CTL. To gain insight into this mechanism, fratricide was induced in a clone of class I-restricted CD8+ CTL by incubating the T cells with their agonist ligand, an octamer peptide derived from chicken ovalbumin. Our results indicate that agonist peptide not only stimulates proliferation and cytolysis of CTL but also initiates signaling pathways that are pertinent to T cell activation, including the mobilization of transcription factors. Also consistent with T cell activation, fratricide induced the transcription and translation of the pro-inflammatory cytokines TNF-α and IFN-γ. Finally, the essential role of perforin, as opposed to Fas/FasL, in fratricide was demonstrated by the selective inhibition of cytolysis with an inhibitor of the perforin pathway, the absence of FasL expression on T cells and the presence of lytic granules visible by electron microscopy. Collectively, these findings reveal that fratricide is mediated by T cell activation and perforin-mediated cytolysis. These results may have implications for the regulation of CD8+ CTL in immune responses.

Original languageEnglish
Pages (from-to)2459-2470
Number of pages12
JournalEuropean Journal of Immunology
Issue number9
StatePublished - Sep 2004
Externally publishedYes


  • Antigens/peptides/epitopes
  • CTL
  • Cytotoxicity
  • Signal transduction


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