Naïve T Cells in the Elderly

Abstract: One of the most striking changes in the primary lymphoid organs during human aging is the progressive involution of the thymus. As a consequence, the rate of naïve T cell output dramatically declines with age and the peripheral T cell pool shrinks. These changes lead to increased incidence of severe infections and decreased protective effect of vaccinations in the elderly. Little is, however, known of the composition and function of the residual naïve T cell repertoire in elderly persons. To evaluate the impact of aging on the naïve T cell pool, we investigated the quantity, phenotype, function, composition, and senescence status of CD45RA⁺CD28⁺ human T cells—a phenotype generally considered as naïve cells—from both young and old healthy donors. We found a significant decrease in the number of CD45RA⁺CD28⁺ T cells in the elderly, whereas the proliferative response of these cells is still unimpaired. In addition to their reduced number, CD45RA⁺CD28⁺ T cells from old donors display significantly shorter telomeres and have a restricted TCR repertoire in nearly all 24 Vβ families. These findings let us conclude that naïve T cells cannot be classified with conventional markers in old age.