Marked increase with age of type 1 cytokines within memory and effector/cytotoxic CD8+ T cells in humans: a contribution to understand the relationship between inflammation and immunosenescence

The ageing process is characterized by a progressive exhaustion of the na ̈ıve T cell reservoir that is accompanied by a compensatory expansion of effector/cytotoxic CD8þCD282 T cells. However, the origin and function of this subpopulation is not completely clarified. In this study, we examined the intracellular cytokine profile in purified CD8þ T cells obtained from 29 healthy subjects of different ages. Type 1 (IFN-g IL-2 and TNF-a) and type 2 (IL-4, IL-6 and IL-10) cytokines were determined in three CD8þ T subsets, i.e. CD952CD28þ (na ̈ıve), CD95þCD282 (effector/cytotoxic), and CD95þCD28þ (memory). As a general trend, we observed, in aged subjects, an increase of type 1 and type 2 intracellular cytokines within the three CD8þ subsets. In particular, we showed that type 1 cytokine-positive cells significantly increased, with age, among all the CD8þ subsets, while a marked increase of type 2 producing cells was observed only in memory CD8þ T cells. These profound changes are compatible with inflame-aging, an hypothesis which suggest that immunosenescence is mainly driven by a chronic antigenic load which not only induces an enormous expansion of CD282 T cells, but also increases their functional activity, exemplified by an high frequency of cells positive for pro-inflammatory cytokines.