Stimulation of Natural Killer Cell Activity and Inhibition of Proliferation of Various Leukemic Cells by Purified Human Leukocyte Interferon Subtypes

Abstract

One of several human leukocyte interferon subtypes A (LeIF-A), obtained in purified form from a gene cloned in Escherichia coli, stimulated human peripheral blood natural killer cell activity, whereas another human leukocyte interferon subtype D (LeIF-D) had no effect with the use of K562 as target cells. With Daudi as target cells, both LeIF-A and LeIF-D stimulated natural killer cell activity. A hybrid human leukocyte interferon, NH₂-terminal 61 amino acids and COOH-terminal 104 residues of LeIF-A and LeIF-D, respectively (LeIF-AD) showed greater stimulation than did LeIF-A, but the stimulation did not exceed that of natural buffy coat interferon. A mixture of equal antiviral units of LeIF-A and LeIF-D was no more effective than was LeIF-A alone. The cloned interferon subtypes showed differential effects on the proliferation of three human leukemic cell lines: Daudi (B-cell lymphoblastoid leukemia); BALL 1 (B-cell acute lymphoblastic leukemia); CCRF-HSB-2 (T-cell acute lymphoblastic leukemia). Growth of Daudi cells was generally most sensitive to all the interferons tested, LeIF-A, -D, -AD, and a buffy coat preparation; no viable cells remained after 120-hr exposure to 1000-unit/ml doses of the interferons. BALL 1 was relatively resistant to the interferon subtypes tested including LeIF-AD, but this cell line was very sensitive to a preparation of natural buffy coat interferon. CCRF-HSB-2 showed some sensitivity to all the interferons with greatest sensitivity to LeIF-A (10% of the viable cells were detected after 1000 units/ml exposure for 120 hr). In contrast to the leukemic cell lines tested, human amnion cells (WISH) and the human erythroid leukemia, K562, were resistant to the antiproliferative activity of the interferons.