Defective natural killer cell activity in B-cell chronic lymphocytic leukaemia is associated with impaired release of natural killer cytotoxic factor(s) but not of tumour necrosis factor-alpha.
The mechanisms accounting for the impaired natural killer cell activity (NKa) in B-cell chronic lymphocytic leukaemia (B-CLL) were investigated in 34 B-CLL patients. We found that patients with B-CLL have indeed very low NKa which may be increased in the presence of recombinant human interferon-alpha or recombinant human interleukin-2. Patients had also very low mitogen-induced cellular cytotoxicity. Their absolute numbers of peripheral blood CD16+, CD57+, CD3+, and CD8+ cells were significantly increased. Patients' NK cells had a normal tumour cell binding capacity but failed to release sufficient amounts of soluble cytolytic molecules upon stimulation with K562 cells or activation with phytohaemagglutinin (PHA). However, B-CLL NK cells released tumour necrosis factor-alpha (TNF-alpha) following stimulation with PHA. We concluded that defective NKa in B-CLL patients is probably the result of an impairment in the production and/or release of soluble cytolytic mediators, but not of TNF-alpha by NK cells. Further studies on the production and release of other cytolytic molecules, such as perforin and granzymes, as well as studies on the possible inability of NK cells to activate the apoptotic mechanisms in the target cells are in progress in our laboratory.
Katrinakis
G
G
Division of Haematology, University of Crete School of Medicine, University Hospital of Heraklion, Greece.
Kyriakou
D
D
Papadaki
H
H
Kalokyri
I
I
Markidou
F
F
Eliopoulos
G D
GD
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002469:Cell Separation; D016009:Chi-Square Distribution; D003601:Cytotoxicity Tests, Immunologic / Q000379:methods; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000276:immunology*; D055646:Killer Factors, Yeast; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011506:Proteins / Q000032:analysis / Q000276:immunology*; D012995:Solubility; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000276:immunology*
D055646:Killer Factors, Yeast; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha