Abstract
Immunosenescence is a natural ageing phenomenon with alterations in innate and especially adaptive immunity and contributes to reduced antimicrobial defence and chronic low-grade inflammation. This is mostly reflected by an increase in organ-directed and/or circulating reactive and cytolytic terminally differentiated T cells that have lost their expression of the costimulatory receptor CD28. Apart from being induced by a genetic predisposition, ageing or viral infections (particularly cytomegalovirus infection), immunosenescence is accelerated in many inflammatory diseases and uraemia. This translates into an enhancement of vascular inflammation and cardiovascular disease varying from endothelial dysfunction to plaque rupture. Emerging data point to a mechanistic role of CD28(null) T cells in glomerulonephritis, where they initiate and propagate local inflammation in concordance with dendritic cells and macrophages. They are suitably equipped to escape immunological dampening by the absence of homing to lymph nodes, anti-apoptotic properties and resistance to suppression by regulatory T cells. Early accumulation of senescent CD28(null) T cells precedes glomerular or vascular injury, and targeting these cells could open avenues for early treatment interventions that aim at abrogating a detrimental vicious cycle.