Significance of senescence for virus-specific memory T cell responses: rapid ageing during chronic stimulation of the immune system

There is a generalized age-related decline in immune responses which leads to increased susceptibility of elderly to infection and, possibly, to autoimmune disease and cancer. This is associated with phenotypic changes of CD8+ T lymphocytes that include the loss of costimulatory molecules CD28 and CD27, which are important for proliferation and cell survival of CD8+ T cells. Loss of these molecules is associated with less ability to respond to recurrent infection. Functional changes within T cells during ageing include a reduction in the number of naïve T cells and a progressively limited T cell repertoire. Furthermore, persistent life-long antigenic stress upon the memory pool leads to telomere erosion and concomittant loss of proliferative capacity, a phenomenon known as replicative senesence. In this review, we discuss that replicative senescence, or clonal exhaustion, may also occur in relatively young individuals, as evidenced from HIV-infected individuals and healthy Ethiopians. We discuss data suggesting that T cell defects may arise in individuals because of chronic antigen activation leading to rapid ageing of the memory CD8+ T cell pool.