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Blood, Vol. 94 No. 11 (December 1), 1999:
pp. 3864-3871
CD38 Triggers Cytotoxic Responses in Activated Human Natural Killer
Cells
Giuseppe Sconocchia,
Julie A. Titus,
Alessandra Mazzoni,
Alberto Visintin,
Federica Pericle,
Stuart W. Hicks,
Fabio Malavasi, and
David M. Segal
From the Experimental Immunology Branch, National Cancer Institute,
National Institutes of Health, Bethesda, MD; and the Institute of
Biology and Genetics, University of Ancona School of Medicine, Ancona,
Italy.
Receptors used by natural killer (NK) cells to mediate natural
cytotoxicity are poorly defined, although it is now clear that a number
of adhesion molecules can serve this function. CD38 transduces signals
on T- and B-cell lines, and we asked whether it could trigger lytic and
secretory responses in human NK cells. By using an anti-CD38 monoclonal
antibody in reverse antibody-dependent cellular cytotoxicity
experiments, it is shown that CD38 engagement triggers cytotoxic
responses by activated NK cells, but not by cytotoxic T
lymphocytes or fresh NK cells. Cross-linking with anti-CD38 F(ab')2 caused activated NK cells to
release granzymes and cytokines, but did not trigger an increase in
intracellular Ca2+. Fresh NK cells acquired
CD38-dependent lytic function during activation with interleukin-2
(IL-2), and inhibitor studies suggested that IL-2 stimulated the de
novo expression of proteins that act between CD38 and the lytic
machinery in NK cells. The induction of proteins that link commonly
expressed adhesion molecules to effector mechanisms could provide a
paradigm for pathogen recognition by the innate immune system.
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