Activation signals leading to proliferation of normal and leukemic CD3+
large granular lymphocytes
JA Aprile, M Russo, MS Pepe and TP Loughran
Clinical Research Division, Fred Hutchinson Cancer Research Center,
Seattle, WA 98104.
The activation signals leading to proliferation of normal and leukemic CD3+
large granular lymphocytes (LGL) were studied in vitro. Anti-CD3 monoclonal
antibody (MoAb) alone (P less than .01) and recombinant interleukin-2
(IL-2) alone (P less than .01) caused significant stimulation of peripheral
blood mononuclear cells (PBMC) from four CD3+ LGL leukemia patients, as
measured in a 3H-thymidine incorporation assay. Recombinant interleukin-4
(IL-4) alone had no effect (P = .11). The combination signals of anti-CD3
MoAb and either IL-2 or IL-4 produced a proliferative response greater than
anti-CD3 MoAb alone (P less than .01) or lymphokine alone (P less than
.01). Leukemic LGL, purified by two-color sorting, were subsequently
activated by anti-CD3 MoAb and IL-2 and assessed for DNA content by viable
Hoechst No. 33342 (HO) staining. Results of these studies demonstrated that
leukemic LGL were stimulated directly by anti-CD3 MoAb and IL-2, with the
percentage of cells in cell cycle (S + G2/M) ranging from 16% to 72%.
Normal CD3+ LGL were also stimulated to enter the cell cycle by anti-CD3
and IL-2. These results show that leukemic LGL proliferate in vitro after
activation through the T-cell receptor and/or lymphokine.
Volume 78,
Issue 5,
pp. 1282-1285,
09/01/1991
Copyright © 1991 by The American Society of Hematology
