Low molecular weight B-cell growth factor and recombinant interleukin-2 are
together able to generate cytotoxic T lymphocytes with LAK activity from
the bone marrow cells of children with acute lymphoblastic leukemia
MX Zhou, HW Findley and AH Ragab
Division of Pediatric Hematology/Oncology, Emory University, Atlanta, GA
30322.
We are reporting here that low-mol wt B-cell growth factor (LMW-BCGF) and
recombinant interleukin-2 (rIL-2) are together able to induce CD3+
cytotoxic T lymphocytes (CTL) with lymphokine-activated killer cell (LAK)
activity from the bone marrow (BM) cells of children with acute
lymphoblastic leukemia (ALL). Ficoll-Hypaque (FH)-separated BM cells were
obtained from patients with active disease (at diagnosis N = 13, in relapse
N = 15) and in complete remission (CR; N = 12). CD3+ cells were removed by
Leu-4 antibody and immunobeads. Cells were cultured (10(5) cells/mL) in
semisolid media with rIL-2 (100 mu/mL), LMW-BCGF (0.1 mu/mL), and the
combination of rIL-2 plus LMW-BCGF, respectively, for seven to ten days.
Pooled colonies were harvested for phenotyping. LMW-BCGF plus rIL-2 induced
large numbers of CD3+ colonies from CD3- precursors. rIL-2 alone did not
induce colony formation. In addition, cells were cultured in liquid media
with LMW-BCGF, rIL-2, and the combination of LMW-BCGF plus rIL-2,
respectively, for seven to 21 days. They were harvested for phenotyping,
and cytotoxicity assays were performed v K562, Raji, and autologous
leukemic cells. LMW-BCGF plus rIL-2 induced significant expansion of CD3+
cells from CD3- precursors, and these cells were activated to kill
autologous leukemic cells in addition to Raji and K562 cell lines. LMW-BCGF
or rIL-2 alone did not induce significant expansion or activation of
cytotoxic CD3- cells. Our hypothesis is that LMW-BCGF plus rIL-2 stimulates
the proliferation and activation of CD3- precursors from the BM cells of
children with acute leukemia to become CD3+ cells that have LAK activity.
This finding may have therapeutic implications.
Volume 74,
Issue 4,
pp. 1355-1359,
09/01/1989
Copyright © 1989 by The American Society of Hematology