International Immunology, Vol 10, 1741-1746, Copyright © 1998 by Oxford University Press
D Nesic, S Henderson and S Vukmanovic
Lysis of target cells (TC) by cytotoxic T lymphocytes (CTL) is achieved by
directional exocytosis of cytolytic molecules-perforin and granzymes. They
are stored within lytic granules which can be readily released following
antigenic stimulation. Secretion of lytic molecules appears to be
controlled by protein kinase C (PKC) activity, since specific modulators of
PKC activity abolish the lysis of TC. We have examined the effect of PKC
modulation on some of the earliest events in the perforin/granzyme-mediated
cytotoxicity. De novo synthesis of perforin mRNA, required for the
refilling of granules and sustained cytotoxicity, seems to be unaltered in
the presence of PKC modulators. Immunofluorescent studies of CTL-TC
conjugates revealed that PKC modulation impairs reorientation of the
microtubule organizing center toward the contact point with the TC, which
accounts for the specific direction of lytic granules exocytosis. Thus, it
appears that PKC regulates exocytosis of lytic granules by governing
microtubule reorganization, one of the initial steps in
perforin/granzyme-mediated cytotoxicity.
ARTICLES
Prevention of antigen-induced microtubule organizing center reorientation in cytotoxic T cells by modulation of protein kinase C activity
Department of Pathology and Kaplan Cancer Center, NYU Medical Center, New York, NY 10016, USA.
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