Journal of Experimental Medicine, Vol 156, 492-505, Copyright © 1982 by Rockefeller University Press
Chemiluminescence response of human natural killer cells. I. The relationship between target cell binding, chemiluminescence, and cytolysis
SL Helfand, J Werkmeister and JC Roder
The binding of tumor cells or fetal fibroblasts to human natural killer
(NK) cells led to a rapid chemiluminescence response within seconds of
target-effector interaction. The degree of chemiluminescence was dependent
on the concentration of NK-enriched lymphocytes or target cells, and plasma
membrane vesicles from K562 also induced a chemiluminescence response. Mild
glutaraldehyde treatment of effector cells abrogated their ability to
generate chemiluminescence, whereas K562 target cells treated in the same
way were almost fully able to induce a chemiluminescence response to
NK-enriched lymphocytes. These results show a directionality of response
with NK as the responders and tumor cells as the stimulators. A survey of
eight different tumor cell lines and fetal fibroblast lines revealed a
striking correlation (r greater than 0.93, P less than 0.001) between the
ability of a given line to bind to NK-enriched lymphocytes, induce
chemiluminescence, and to be lysed. Three differentiated sublines of K562
grown in butyrate and cloned induced little chemiluminescence compared with
the K562 parent, and they were selectively resistant to NK-mediated binding
and cytolysis. In addition, treatment of K562 cells with higher
concentrations of glutaraldehyde for longer periods led to varying degrees
of target antigen preservation, as measured in cold target competition
assays and in conjugate formation. The degree of NK target antigen
preservation correlated directly with the ability of the cells to induce
chemiluminescence (r greater than 0.95). The degree of NK activation was
also important because interferon-pretreated effectors generated more
chemiluminescence upon stimulation with K562 or MeWo targets. Monocytes or
granulocytes did not contribute to the chemiluminescence induced by
NK-sensitive targets. Some NK-resistant tumor cell lines were sensitive to
monocyte-mediated cytolysis and also induced chemiluminescence in monocytes
but not NK cells. These results show that the target structures recognized
by the NK cell may play a role in NK activation because the degree of
chemiluminescence was directly proportional to the ability of a given
target cell line to bind to the NK cell and to be lysed.
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