Activation-induced cell death of T-cells in elderly

Abstract

The elimination of expanded T-cells at the end of immune response is crucial to maintain homeostasis and avoid any uncontrolled inflammation. Resting mature T-lymphocytes when activated via their antigen-specific receptor (TCR) and CD28 coreceptor start to proliferate and acquire resistance to apoptosis. Reactivation of T-cells induces expression of CD95L which after binding to CD95 surfaceexpressed death receptor triggers signaling pathway to apoptosis. The process is named Activation-Induced Cell Death-AICD. However, in executing AICD death receptor-dependent apoptotic pathway (extrinsic) can overlap with mitochondrial (intrinsic) signaling to apoptosis. Immunosenescence leads to the shrinkage of T-cell repertoire due to the reduction of naïve cells and accumulation of oligoclonal CD8+ and to a lower extent CD4+ cells, which are mainly CD95-positive and CD28-negative. Also, propensity to undergo apoptosis changes with age. However, data so far collected are inconclusive as they show an increased, unchanged or decreased propensity to AICD in the elderly in comparison with young individuals.