T Cells, Aging and Senescence

The T cell compartment undergoes characteristic changes with age, which contribute to increased incidence and severity of infections and reduced immunogenicity and efficacy of many vaccines in the older population. Production of naïve T cells is severely impaired due to a decreased output of lymphoid cells from the bone marrow and the involution of the thymus. At the same time, antigen-experienced, highly differentiated T cells accumulate resulting in a diminished T cell receptor repertoire. These cells show some similarities with senescent cells, such as shorter telomers, accumulated DNA damage and metabolic changes. Latent infection with Cytomegalovirus also impacts the T cell compartment and aggravates several of its age-associated changes. Loss of CD28 expression is one hallmark of T cells after repeated antigenic stimulation, but CD28 T cells cannot be considered truly senescent as e.g. they are still able to proliferate upon adequate stimulation. Several additional markers have been suggested in order to define a potential fully senescent T cell population, but no consensus definition has been reached so far. It has been postulated that highly differentiated senescent-like T cells are unable to eliminate other senescent cell types. Removal of senescent non-immune cells has been shown to be beneficial for the organism and a reliable definition of senescent T cells is essential for an extension of this concept to T cells.