TCR alpha/beta and TCR gamma/delta CD4-/CD8- HLA-DR alloreactive CTL clones do not use Fas/Fas ligand pathway to lyse their specific target cells

Hum Immunol. 1996 Nov;51(1):13-22. doi: 10.1016/s0198-8859(96)00164-4.

Abstract

The expression of Fas Ligand (FasL) on human TCRalpha/beta and TCRgamma/delta CD4-/CD8- MHC class II-alloreactive clones and Fas/FasL-mediated cytotoxicity were investigated. These clones mediated a HLA-DR2-restricted cytotoxicity toward E418 B cell line (Fas+). Northern blot analysis demonstrated that all the clones expressed FasL mRNA upon stimulation with E418 specific target. FasL surface expression was detected by immunofluorescence analysis using Fas-Fc soluble protein as well as anti-FasL polyclonal antibodies. Cytotoxicity experiments performed in the presence of anti-Fas, anti-FasL and Fas-Fc molecule indicated that these reagents were unable to inhibit T cell clone mediated lysis toward E418. In addition, when emetine, known to inhibit the induction of Fas-mediated killing, was added during the cytolysis effector phase, no inhibition was observed. These data strongly suggest that Fas/FasL pathway is not involved in this particular T-cell clone-mediated lysis. This cytotoxicity is extracellular Ca(2+)-dependent and is abolished in the presence of EGTA suggesting that it is mainly perforin/granzyme-based.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4 Antigens / analysis*
  • CD8 Antigens / analysis*
  • Cell Line
  • Clone Cells
  • Cytotoxicity, Immunologic*
  • Humans
  • Ligands
  • Receptors, Antigen, T-Cell, alpha-beta / analysis*
  • Receptors, Antigen, T-Cell, gamma-delta / analysis*
  • T-Lymphocytes, Cytotoxic / immunology*
  • fas Receptor / physiology*

Substances

  • CD4 Antigens
  • CD8 Antigens
  • Ligands
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Antigen, T-Cell, gamma-delta
  • fas Receptor