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

A. Rosato, A. Zambon, S. Mandruzzato, V. Bronte, B. Macino, F. Calderazzo, D. Collavo, P. Zanovello

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)294-305
Number of pages12
JournalCellular Immunology
Volume159
Issue number2
DOIs
Publication statusPublished - 1994

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

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