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 cros
slinking leads to activation of the lytic process which includes conju
gate formation, lethal hit delivery, and events leading to target cell
death. We studied the role of PTKs in antigen-specific cytotoxicity e
xerted by both in vivo activated and in vitro maintained CTL. We found
that the PTK inhibitors herbimycin A and genistein blocked T-cell-med
iated 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 turn
over, thus indicating that PTK activity is an obligatory event for the
activation of antigen-specific CTL effector function. (C) 1994 Academ
ic Press, Inc.