PERFORINS IN HUMAN CYTOLYTIC CELLS - THE EFFECT OF AGE

The ageing process is associated with a progressive increase in the nu mber of circulating NK cells, together with a decreased lytic activity per cell. A similar decrease in activity was also found for CD8 lymph ocytes. Cytotoxic T- and NK cells express cytoplasm granules containin g cytolytic effector molecules (as perforins, studied here) which can recognize and destroy damaged, infected and/or mutated target cells. T o investigate whether an altered distribution of perforins in cytolyti c cells or a reduced number of cytolytic cells producing perforins und erlies decreased cytolytic activity with advancing age, perforin expre ssion was assessed at the single cell level in T- (CD4 and CD8) and NK (CD16) peripheral blood lymphocytes from elderly subjects by flow cyt ometry. Perforin distribution at the cellular level in CD8+ and CD16cell cytoplasm suggested a similar distribution during ageing and a si milar number of cells producing perforins. In addition, perforin utili zation was maintained in the generation of cytolytic activity against K562 target cells and perforin synthesis in culture following activati on was unabated. These data stress the importance of other factors, su ch as defective signal transduction for granule exocytosis, that may a ccount for the different pattern of lytic activity found in aged peopl e. (C) 1996 Elsevier Science Ireland Ltd.