Abstract The IL-7 receptor alpha (IL-7Rα) is the high affinity receptor for IL-7 which is essential for T cell homeostasis. We recently reported an age-associated expansion of human effector memory (EM) CD8+ T cells expressing IL-7Rα low (IL-7Rαlow), which could be detrimental to hosts by occupying “immunological space”. We investigated the potential mechanisms for this phenomenon, focusing on cytomegalovirus (CMV) infection and INF-α. In the elderly (age⩾65), CMV infection was associated with a decreased frequency of naïve CD8+ T cells as well as with an increased frequency of total EM and IL-7Rαlow EM CD8+ T cells. However, in the young (age⩽40), this viral infection was associated only with an increased frequency of IL-7Rαlow EM CD8+ T cells. There was no association found between CMV immune status and plasma levels of IFN-α. In CMV-infected young and elderly people, INF-α levels had no correlation with the frequency of IL-7Rαlow EM CD8+ T cells although this cytokine levels correlated with the frequency of IL-7Rαlow CD45RA+ EM CD8+ T cells in CMV-uninfected elderly people. Our findings suggest that the effect of CMV infection on the frequency of CD8+ T cell subsets may begin with IL-7Rαlow EM CD8+ T cells and spread to other subsets with aging. Also, IFN-α could be associated with the expansion of IL-7Rαlow CD45RA+ EM CD8+ T cells in the CMV-uninfected elderly.