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 human leukocyte interferon subtype D (LeIF-D) had no effect with the use of human erythroid leukemia 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 3 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 h exposure to 1000-U/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 U/ml exposure for 120 h). In contrast to the leukemic cell lines tested, human amnion cells (WISH) and K562 were resistant to the antiproliferative activity of the interferons.