CHARACTERIZATION OF A CELL-LINE, NKL, DERIVED FROM AN AGGRESSIVE HUMAN NATURAL-KILLER-CELL LEUKEMIA

Cell line NKL was established from the peripheral blood of a patient w ith CD3(-)CD16(+)CD56(+) large granular lymphocyte (LGL) leukemia. The neoplastic LGL of this patient mediated natural killing and antibody- dependent cellular cytotoxicity (ADCC) and exhibited proliferative res ponses similar to normal CD16(+)CD56(dim) natural killer (NK) cells. T he morphology of NKL cells resembles that of normal activated NK cells . The karyotype of NKL is 47, XY, add (1) (q42), +6, del (6) (q15 q23) , del (17) (p11). NKL cells express CD2, CD6, CD11a, CD26, CD27, CD29, CD38, CD43, CD58, CD81, CD94, CD95, class II MHC, and the C1.7.1 anti gen, but do not express detectable levels of CD3, CD4, CD5, CD8, CD14, CD19, CD20, CD28, alpha/beta or gamma/delta T cell receptors on the c ell surface. The density of the CD16, CD56, and CD57 antigens declined markedly on NKL cells during prolonged in vitro culture. Nevertheless , NKL cells can mediate ADCC as well as natural killing. NKL cells are strictly dependent on interleukin-2 (IL-2) for sustained growth and d ie if deprived of IL-2 for more than 7 days. NKL cells proliferate in response to concentrations of IL-2 as low as 1 pM, but an optimal prol iferative response requires similar to 100 pM IL-2. NKL cells growing in the presence of IL-2 express abundant IL-2R alpha with little or no detectable IL-2 beta or gamma chain on the cell surface; NKL cells de prived of IL-2 express high levels of both IL-2R alpha, and beta. IL-4 , IL-7, and IL-12, unlike IL-2, do not maintain the viability of NKL c ells. Furthermore, IL-1, IL-4, IL-6, IL-7, IL-12, tumor necrosis facto r-alpha (TNF-alpha), interferon-alpha (IFN-alpha), and IFN-gamma do no t support the growth of NKL cells. The NKL cell Line may prove useful for studies of human NK cell biology.