Several lines of evidence point to a central role for protein tyrosine kinases (PTKs) in the signal transduction cascade initiated by T-cell receptor (TCR) engagement. In cytotoxic T lymphocytes (CTL), TCR crosslinking leads to activation of the lytic process which includes conjugate formation, lethal hit delivery, and events leading to target cell death. We studied the role of PTKs in antigen-specific cytotoxicity exerted by both in vivo activated and in vitro maintained CTL. We found that the PTK inhibitors herbimycin A and genistein blocked T-cell-mediated lysis in a dose-dependent manner. Lack of cytotoxic function was not due to abrogation of conjugate formation, but was associated with inhibition of both granule exocytosis and phosphatidylinositides turnover, thus indicating that PTK activity is an obligatory event for the activation of antigen-specific CTL effector function.

Inhibition of protein tyrosine phosphorylation prevents T-cell-mediated cytotoxicity.

Bronte, Vincenzo;
1994-01-01

Abstract

Several lines of evidence point to a central role for protein tyrosine kinases (PTKs) in the signal transduction cascade initiated by T-cell receptor (TCR) engagement. In cytotoxic T lymphocytes (CTL), TCR crosslinking leads to activation of the lytic process which includes conjugate formation, lethal hit delivery, and events leading to target cell death. We studied the role of PTKs in antigen-specific cytotoxicity exerted by both in vivo activated and in vitro maintained CTL. We found that the PTK inhibitors herbimycin A and genistein blocked T-cell-mediated lysis in a dose-dependent manner. Lack of cytotoxic function was not due to abrogation of conjugate formation, but was associated with inhibition of both granule exocytosis and phosphatidylinositides turnover, thus indicating that PTK activity is an obligatory event for the activation of antigen-specific CTL effector function.
1994
Animals; Benzoquinones; Cell Death; immunology; Cytotoxicity; Immunologic; drug effects/immunology; DNA; metabolism; Esterases; Flow Cytometry; Genistein; Inositol Phosphates; biosynthesis; Isoflavones; pharmacology; Lactams; Macrocyclic; Mice; Inbred DBA; Protein-Tyrosine Kinases; antagonists /&/ inhibitors/physiology; Quinones; T-Lymphocytes; Cytotoxic; Tumor Cells; Cultured
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/360023
Citazioni
  • ???jsp.display-item.citation.pmc??? 1
  • Scopus 8
  • ???jsp.display-item.citation.isi??? 9
social impact