Perforins in human cytolytic cells: the effect of age

The ageing process is associated with a progressive increase in the number of circulating NK cells, together with a decreased lytic activity per cell. A similar decrease in activity was also found for CD8 lymphocytes. Cytotoxic T- and NK cells express cytoplasm granules containing cytolytic effector molecules (as perforins, studied here) which can recognize and destroy damaged, infected and/or mutated target cells. To investigate whether an altered distribution of perforins in cytolytic cells or a reduced number of cytolytic cells producing perforins underlies decreased cytolytic activity with advancing age, perforin expression was assessed at the single cell level in T- (CD4 and CD8) and NK (CD16) peripheral blood lymphocytes from elderly subjects by flow cytometry. Perforin distribution at the cellular level in CD8+ and CD16+ cell cytoplasm suggested a similar distribution during ageing and a similar number of cells producing perforins. In addition, perforin utilization was maintained in the generation of cytolytic activity against K562 target cells and perforin synthesis in culture following activation was unabated. These data stress the importance of other factors, such as defective signal transduction for granule exocytosis, that may account for the different pattern of lytic activity found in aged people.