AGE-DEPENDENT DECREASES OF NK CELL PHOSPHOINOSITIDE TURNOVER DURING SPONTANEOUS BUT NOT FC-MEDIATED CYTOLYTIC ACTIVITY

The progressive increase in the number of peripheral NK cells found in the elderly does not correlate with a corresponding increase in lytic activity, On the contrary, a decreased function of circulating NK cel ls purified from old subjects was observed on a per cell basis, Most o f the studies on NK cells have focused on late events such as lytic ac tivity, In view of this, little is currently known about the modificat ion of the early signalling pathways of NK cells in elderly people, Th is study investigated whether the modification of NK lytic activity co uld be related to differences in the metabolic pattern of activation o f these cells in the elderly, NK cells were negatively purified by imm unomagnetic depletion from the peripheral blood of selected old and yo ung healthy subjects. Hydrolysis of inositol phospholipids was measure d following incubation with K562 target cells and/or CD16 mAb for diff erent times, Our data show that there is a pronounced age-related decr ease in the ability to generate total inositol monphosphates and, part icularly, inositol trisphosphates by NK cells following K562 stimulati on (spontaneous cytolytic activity) together with an attenuated and de layed hydrolysis of phosphatidylinositol bisphosphate, while phosphoin ositide turnover is preserved following Fc triggering (antibody-depend ent cell-mediated cytotoxicity), These results confirm that, also in o ld subjects, different biochemical pathways of activation are involved in NK cells when target or antibody-mediated triggering occurs and ma y aid the development of experimental and therapeutic strategies to co unteract declines in cell mediated immune functions associated to adva ncing age.