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CTLs lyse Fas-expressing target cells by the concomitant action of a perforin- and a Fas-dependent mechanism. This study analyzed whether target cells pulsed with T cell antagonists and other altered peptide ligands (APLs) were susceptible selectively to only one of these two mechanisms. In vivo and in vitro activated T cells from transgenic mice expressing a TCR specific for lymphocytic choriomeningitis virus were used as effector cells. To distinguish between perforin- and Fas-dependent cytotoxicity, T cells from normal or perforin-deficient mice were used to lyse peptide-pulsed Fas-positive or Fas-negative target cells. In contrast to previous reports that have shown that APLs selectively induce the Fas-dependent pathway of cytotoxicity, our results demonstrate that target cells pulsed with T cell antagonists and other APLs are lysed predominantly by the perforin-dependent pathway. The contribution of Fas-mediated cytotoxicity was similar for the full agonist and the APLs. Thus, full agonists, partial agonists, and antagonists trigger similar and not distinct pathways of cytotoxicity.

Type

Journal article

Journal

Journal of immunology (Baltimore, Md. : 1950)

Publication Date

11/1997

Volume

159

Pages

4165 - 4170

Addresses

Department of Medical Biophysics, Ontario Cancer Institute, Canada. bachmann@oci.utoronto.ca

Keywords

T-Lymphocytes, Cytotoxic, Animals, Mice, Transgenic, Mice, Membrane Glycoproteins, Receptors, Antigen, T-Cell, Cell Death, Cytotoxicity, Immunologic, Pore Forming Cytotoxic Proteins, Fas Ligand Protein, Perforin, fas Receptor