Induction of NK activity in large granular lymphocyte leukemia: activation
with anti-CD3 monoclonal antibody and interleukin 2
TP Loughran , KE Draves, G Starkebaum, P Kidd and EA Clark
Large granular lymphocyte (LGL) leukemia is a rare disease characterized by
clonal expansion of LGL associated with chronic neutropenia, multiple
auto-antibodies, and occasionally polyarthritis. We studied cell surface
antigen expression and functional activity of leukemic LGL from ten such
patients. Using two-color flow cytometric analysis, we found that leukemic
LGL from all ten patients expressed the CD3 and HNK-1 markers, while cells
from only four patients expressed IgG Fc receptors (FcR). The LGL leukemic
cells had little or no NK activity (defined as MHC-nonrestricted
cytotoxicity against K562 target cells); however, NK activity could be
induced in leukemic LGL by in vitro treatment with as little as 0.05
microgram/mL of anti-CD3 monoclonal antibody. Cell sorting experiments
demonstrated that NK activity was induced in CD3+ leukemic LGL (either
CD3+, HNK-1+ or CD3+, FcR+) with anti-CD3 monoclonal antibody but not in
normal CD3+, FcR- T cells. Treatment with purified interleukin 2 (IL 2)
also caused direct activation of some CD3+ leukemic LGL. Despite induction
with anti-CD3 MAb or IL 2, activated leukemic LGL did not proliferate or
express high density IL 2 receptors detectable by cell sorter analysis.
Treatment with alpha interferon had minimal effect on NK activity of LGL
leukemic cells. These results suggest that leukemic LGL may provide a
useful model for examining the signals required for LGL maturation and
activation.
Volume 69,
Issue 1,
pp. 72-78,
01/01/1987
Copyright © 1987 by The American Society of Hematology
