Lymphokine-activated killer cell functions in patients with leukemic B-
lymphoproliferative diseases
D van der Harst, A Brand, SA van Luxemburg-Heys, EM Kooy-Winkelaar and JJ van Rood
Department of Immunohematology and Blood Bank, University Medical Center,
Leiden, The Netherlands.
Nine patients with leukemic B-lymphoproliferative diseases (B-LPD) were
evaluated for development of in vitro recombinant interleukin-2 (rIL-2)-
activated killer (LAK) cells. B-cell cultures were established from
peripheral blood mononuclear cells (PBMNCs) containing 63% +/- 29%
malignant cells. Short-term cultures were tested after 5-day activation
with 500 U rIL-2/mL. Long-term cultures were maintained for 4 to 6 weeks by
weekly addition of 500 U rIL-2 and autologous irradiated feeder cells. In
the first week, the cells decreased considerably in the long-term cultures
but thereafter cells proliferated (mainly T cells) on the average 300-fold
(range 30- to 1,000-fold). In the short- term cultures, there was a 36%
reduction of malignant B cells. In long- term cultures, B cells were
reduced from 63% to 8%; three cultures still contained greater than 15% B
cells. The CD16-positive cell percentage was comparable in both types of
cultures and ranged from 2% to 17%. Effector cells lysing the natural
killer (NK)-sensitive cell line K562 could be induced in all patients.
Except in patients with chronic lymphocytic leukemia (CLL) and high
malignant cell numbers, NK activity was already restored after 5 days.
Optimal NK activity was obtained after 1.5 to 2.5 weeks. LAK cells killing
NK-resistant lymphoma cell lines showed optimal activity after 2 to 3 weeks
of culture. However, LAK cells killing greater than 10% of autologous
malignant cells were obtained in only one third of the patients. The
discrepancy between strong cytolytic activity against the NK-sensitive
(K562) target cells obtained in all patients and the cytotoxic activity
against NK-resistant cell lines contrasts with the poor development of LAK
cells against autologous tumor cells. This discrepancy does not appear to
be explained by soluble inhibitory factors released during the tumor
cultures, as allogeneic LAK cells were not inhibited by supernatants from
patients' cultures. Further investigations are warranted to reveal
cell-mediated inhibition by tumor cells or suppressor cells.
Volume 74,
Issue 7,
pp. 2464-2470,
11/15/1989
Copyright © 1989 by The American Society of Hematology
