CD28− T cells: their role in the age-associated decline of immune function

The accumulation of CD28− T cells, particularly within the CD8 subset, is one of the most prominent changes during T-cell homeostasis and function associated with aging in humans. CD28, a major co-stimulatory receptor, is responsible for the optimal antigen-mediated T-cell activation, proliferation and survival of T cells. CD28− T cells exhibit reduced antigen receptor diversity, defective antigen-induced proliferation and a shorter replicative lifespan while showing enhanced cytotoxicity and regulatory functions. Gene expression analyses reveal profound changes of CD28− T cells in comparison to their CD28+ counterparts and corroborate their functional differences. Here we review recent advances in our understanding of CD28− T cells and their role in the age-associated decline of immune function.