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Mechanisms accounting for the defective natural killer activity in patients
with hairy cell leukemia
L Trentin, R Zambello, C Agostini, A Ambrosetti, T Chisesi, R Raimondi, P Bulian, G Pizzolo and G Semenzato
Padua University School of Medicine, Department of Clinical Medicine,
Italy.
Natural killer (NK) cell activity is severely impaired in untreated
patients with hairy cell leukemia (HCL). In an attempt to investigate
whether this impairment is related to a defect at the target cell binding
and/or at the post target cell binding level, we evaluated the peripheral
blood mononuclear cells (PBMC) of HCL patients for their ability to: (1)
bind and kill K-562 NK-sensitive targets at the single cell binding level;
(2) release the NK cytotoxic factor (NKCF) under different in vitro
stimuli, including K-562 and phytohemoagglutinin; and (3) kill K-562
targets in a lectin-dependent cellular cytoxicity (LDCC) assay. This study
demonstrates that untreated HCL patients' PBMC show a low ability to form
conjugates with K-562 targets at the single cell binding level (5.7% +/-
1.0%) with respect to patients studied after treatment (9.3% +/- 1.3%) and
controls (15.0% +/- 4.0%); P less than .05 and P less than .001,
respectively. A decreased ability to kill the bound target was demonstrated
in untreated cases (1.2% +/- 1.1%) versus patients studied after treatment
and controls (12.3% +/- 1.6%, 17.0% +/- 3.1% respectively); P less than
.001 in both conditions. After activation of effector cells with
interleukin-2 (IL- 2) in vitro, an increase in the ability of PBMC to form
conjugates with K-562 targets and kill the bound target was demonstrated in
each group of patients. Moreover, IL-2 was able to increase the
cytotoxicity against NK-sensitive targets in all patients tested.
Evaluation of NKCF production showed that untreated patients release low
levels of NKCF when PBMC were incubated in the presence of K-562
stimulators (1.8% +/- 0.7%) with respect to patients after interferon-alpha
(IFN-alpha) therapy (7.6% +/- 2.1%) and controls (12.9% +/- 2.2%); P less
than .02 and P less than .001, respectively. When the recognition
mechanisms were bypassed by triggering the cells with lectins in an LDCC
assay, we demonstrated an increase of the lytic activity in both groups of
patients with respect to the baseline values. However, the cytotoxic
capacity observed in untreated patients was significantly lower than that
observed in subjects after IFN-alpha therapy and controls (P less than
.001). These findings suggest that the impaired NK activity observed in
patients with HCL is related to defects both at the target and posttarget
cell binding levels.
Volume 75,
Issue 7,
pp. 1525-1530,
04/01/1990
Copyright © 1990 by The American Society of Hematology
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