IMPAIRED RELEASE OF NATURAL-KILLER CYTOTOXIC FACTOR(S) BY PERIPHERAL-BLOOD LYMPHOCYTES IN PATIENTS WITH CHRONIC LGL-PROLIFERATIVE DISEASE

Background. Chronic LGL-proliferative disease (LGL-PD) is a clonal exp ansion of cells with large granular lymphocyte (LGL) morphology. In mo st cases, proliferating cells express both suppressor/cytolytic T-cell and natural killer (NK) cell surface markers, but other cell phenotyp es may be observed. LGL-PD lymphocytes have been found to lack or show very low natural killer cell activity (NKa). The aim of the present p aper is to investigate the underlying mechanisms responsible for impai red NKa in a homogeneous group of five selected LGL-PD patients with a CD3+, CD8+, CD57+ cell phenotype. Results. In all patients, the expan ded cell population expressed very low NKa against K562 cell targets, but this increased significantly with recombinant human interleukin-2 (rhIL-2) and phytohemagglutinin (PHA) activation. Recombinant human al pha-interferon (rhIFN-alpha) had no significant effect on NKa. Cells d isplayed normal tumor cell binding capacity but failed to release suff icient amounts of functionally active natural killer cytotoxic factor( s) (NKCFs) upon interaction with the NK-sensitive K562 cells targets. However, they did release soluble cytolytic molecules against K562 cel ls upon activation with PHA. Conclusions. Our findings provide evidenc e that the defective NKa in LGL-PD patients with the aforementioned ph enotype is probably due, at least in part, to the inability of expande d lymphocytes to release NKCFs upon interaction with NK-sensitive cell targets. Since recognition of target cells by patient lymphocytes is not disturbed and the cells are capable of producing NKCFs upon activa tion with PHA, it is probable that the cause of this abnormality is lo cated at the level of the activation signal provided by the stimulator y target cells. Studies in subcellular level are certainly needed for a more precise determination of the underlying defect.