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Cancer Research Unit, Canberra Hospital, Canberra, Australia
CD16 (Fc
RIIIA), the low affinity receptor for IgG, is expressed
on the majority of human peripheral blood NK cells. Ligation of CD16
with mAb or immune complexes activates NK cell cytotoxicity and
cytokine secretion, and stimulates death of activated NK cells by
apoptosis. This study uses NK cells labeled with the stable
intracytoplasmic fluorescent dye 5- and 6-carboxyfluorescein diacetate
succinimidyl ester to provide quantitative data on the effect of CD16
ligation on NK cell division and NK cell survival. When NK cells are
cultured with rIL-2 and CD16 is ligated, NK cell division is
stimulated, but there also is a substantial loss of NK progenitor
cells. When NK cell proliferation is stimulated by coculture with
-irradiated MM-170 malignant melanoma cells and rIL-2, CD16 ligation
enhances entry of NK cells into division. In some cases, CD16 ligation
is essential for NK cell proliferation stimulated by MM-170 cells. In
these cultures, there is no loss of NK progenitor cells. This study
demonstrates that CD16 is an activation receptor for NK cell
proliferation, and suggests that cellular costimulation alters the
balance between NK cell death and NK cell proliferation stimulated by
CD16 ligation.
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