???? T cells represent a subset of unconventional T lymphocytes that are known for their reactivity against different pathogens and considered as intermediate mediators between adaptive and innate immunity. We provide in this paper further insights underlying the changes that affect the ???? T cell compartment with advanced age in humans. We show that both aging and CMV infection impact independently on the ???? T cell compartment. Most ???? T cells are significantly affected by age and present a decreased frequency in the elderly. The decline of the ???? T cell pool appears to be independent from the activity of the thymus, arguing in favor of an extrathymic site of ???? T cell production in humans. Of note, CMV infection, which is directly associated with the activation of the pool of V??2(-) ???? T cells, promotes nonetheless the inflation of this compartment throughout life. CMV seropositivity accentuates further the accumulation of highly differentiated lymphocytes in V??2(-) ???? T cell subsets with time, in contrast to V??2(+) ???? T cells, which maintain a less differentiated phenotype. This is similar to the effect of CMV on ???? T cells and suggests that ???? T cells may vary in differentiation phenotype according to distinct stimuli or pathogens.