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Human large granular lymphocytes: Spontaneous and interferon-boosted NK activity against adherent and nonadherent tumor cell lines

Abstract:

Human natural killer (NK) cells against K-562 tumor cells have been morphologically identified as large granular lymphocytes (LGL). We have investigated whether LGL are also responsible for NK activity against a variety of adherent and nonadherent tumor cell lines. LGL-enriched fractions, obtained by centrifugation of nonadherent mononuclear cells on discontinuous density gradients of Percoll, contained high levels of spontaneous and interferon- (IFN) boosted NK activity against each of the target cells tested. In contrast, the LGL-depleted fractions, which contain most of the typical small lymphocytes, were devoid of NK activity and did not develop appreciable activity after treatment with IFN. The ability of the different fractions to exert NK activity correlated with their capacity to form conjugates with nonadherent tumor cells. Reconstitution of the different fractions with macrophages did not increase the NK activity of already cytotoxic fractions and did not induce appreciable activity in the LGL-depleted fractions. On the other hand, mixtures of highly cytotoxic and nonreactive cell fractions did not reveal the presence of suppressor cells for NK in the nonreactive fractions. Taken together, our data demonstrate that both spontaneous and IFN-boosted NK activity is confined to the LGL-enriched fractions and suggest that LGL are the main effector cells exerting NK cytotoxicity against a variety of adherent as well as nonadherent tumor cell lines.