Production of colony-stimulating activity by human natural killer cells:
analysis of the conditions that influence the release and detection of
colony-stimulating activity
V Pistoia, S Zupo, A Corcione, S Roncella, L Matera, R Ghio and M Ferrarini
Servizio di Immunologia Clinica, Istituto Nazionale per la Ricerca sul
Cancro, Genova, Italy.
Highly purified natural killer (NK) cell suspensions were tested for their
capacity to release colony-stimulating activity (CSA) in vitro. NK cell
suspensions comprised primarily CD16+ cells and were devoid of CD3+ T
cells, CD15+ monocytes, and of B cells. CSA was detected in the NK cell
supernatants and sustained the growth of myeloid colonies from both normal
peripheral blood and bone marrow. CSA could be in part inhibited by
pretreating NK cell culture supernatants with a specific goat
anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antiserum.
The inhibition, however, was never complete, a finding that suggests that
additional factors were responsible for CSA. Incubation of NK cells with
K562 cells (an NK-sensitive target) or with normal bone marrow cells
resulted in the appearance of a strong colony- inhibiting activity (CIA) in
the culture supernatants. Such CIA was demonstrable in an experimental
system where bone marrow or peripheral blood progenitors were induced to
form myeloid colonies in the presence of conditioned medium by
CSA-producing giant cell tumor (GCT) cells. Stimulation of NK cells with
NK-insensitive targets failed to induce CIA production. Neutralizing
antitumor necrosis factor (TNF) monoclonal antibodies (MoAbs) were found
capable of inhibiting CIA present in the supernatants of NK cells
stimulated with K562 cells. Following treatment with anti-TNF antibodies,
CSA was again detectable in the same supernatants. This finding indicates
that induction of TNF production did not concomitantly switch off CSA
production by NK cells. Pretreatment of NK cells with recombinant
interleukin-2 (rIL-2) or gamma interferon (r gamma IFN) did not change the
amount of CSA released. However, treatment with rIL-2 caused the appearance
of a factor in the NK cell supernatants capable of sustaining the formation
of colonies of a larger size.
Volume 74,
Issue 1,
pp. 156-164,
07/01/1989
Copyright © 1989 by The American Society of Hematology
