DEFECTIVE NATURAL-KILLER-CELL ACTIVITY IN B-CELL CHRONIC LYMPHOCYTIC-LEUKEMIA IS ASSOCIATED WITH IMPAIRED RELEASE OF NATURAL-KILLER CYTOTOXIC FACTOR(S) BUT NOT OF TUMOR-NECROSIS-FACTOR-ALPHA

The mechanisms accounting for the impaired natural killer cell activit y (NKa) in B-cell chronic lymphocytic leukaemia (B-CLL) were investiga ted in 34 B-CLL patients. We found that patients with B-CLL have indee d very low NKa which may be increased in the presence of recombinant h uman interferon-alpha or recombinant human interleukin-L Patients had also very low mitogen-induced cellular cytotoxicity. Their absolute nu mbers of peripheral blood CD16+, CD57+, CD3+, and CD8+ cells were sign ificantly increased, Patients' NK cells had a normal tumour cell bindi ng capacity but failed to release sufficient amounts of soluble cytoly tic molecules upon stimulation with K562 cells or activation with phyt ohaemagglutinin (PHA). However, B-CLL NK cells released tumour necrosi s factor-alpha (TNF-alpha) following stimulation with PHA. We conclude d that defective NKa in B-CLL patients is probably the result of an im pairment in the production and/or release of soluble cytolytic mediato rs, but not of TNF-alpha by NK cells. Further studies on the productio n and release of other cytolytic molecules, such as perforin and granz ymes, as well as studies on the possible inability of NK cells to acti vate the apoptotic mechanisms in the target cells are in progress in o ur laboratory.