Aged-related shifts in T cell homeostasis lead to intrinsic T cell defects

Our recent studies indicate that the longer peripheral persistence of naïve CD4 T cells that occurs with age is necessary for the development of the key aging defects that lead to compromised responses to vaccination and to new pathogens or new strains of circulating infectious agents. This longer persistence is in turn is linked to the decrease in development of new thymic emigrants and thymic involution that occur at adolescence. Therefore the process of development of naïve CD4 aging defects, is closely tied to the homeostasis of T cells and the shifts that occur in their homeostasis with age. Here we review this connection between age-related changes in T cell homeostasis and the development of T cell defects and discuss the implication for approaches to better vaccinating the elderly.

► Naïve T cells become less able to engage in effective immune responses with aging.
► Reduced production of naïve T cells with age is balanced by a longer lifespan.
► Reduction in Bim expression is associated with extended lifespan of naïve T cells.
► A longer lifespan facilitates development of age-related defects among naïve T cells.
► Alternative vaccination strategies may be able to overcome these defects.