Figure 1.

Age-associated changes in T cell generation and function throughout the lifespan. The T cell landscape is in flux throughout life, shaped by age-associated changes in T-cell subset composition and function, which are influenced by cell-intrinsic factors as well as microenvironmental cues that support T cell development and differentiation. While the perinatal T cell pool is dominated by naive conventional T cells (Tconv) and recent thymic emigrants (RTEs), the aged T cell pool contains a higher proportion of memory T cells. Perinatal and aged T cells share several striking similarities in phenotypes and functions. The perinatal and aged CD8+ Tconv cells, including virtual memory T cells (Tvm), are shifted towards short-lived, innate-like, effector responses characterized by increased proliferative potential and rapid cytokine production, at the expense of long-lasting memory generation. Naive CD4+ T cells also display age-associated changes at both ends of the age spectrum, such as reduced T cell receptor (TCR) responsiveness and IL-2 production. In addition, T cells are more self-reactive both early and late in life, which may reflect age-associated changes in thymic selection and/or peripheral maintenance. Regulatory T cells (Treg) generation in the thymus peaks in the perinatal period, but Tregs at both ends of the age spectrum have superior suppressive capacity compared to adult Tregs. These age-associated changes implicate the thymic microenvironment in selecting Tconv cells and Tregs that cater to rapidly changing immune challenges throughout life, while at the same time curbing the risk of triggering autoimmunity. T cell output from the thymus is also lower in both fetal/neonatal periods as well as in the elderly. The uneven pattern of thymic output depicted in the histogram reflects variability throughout life due to numerous extrinsic stressors, such as infections and pregnancy, that alter thymic cellularity and output. In keeping with the above similarities between T cells in the perinatal and elderly stages, immune outcomes, such as overall responsiveness to vaccines and pathogens, as well susceptibility to new onset autoimmunity change in similar directions at both extremes of the lifespan. Phenotypes with question marks are yet to be defined clearly, and dotted lines indicate variable findings in the indicated attributes. All features have been reported in both humans and mice, except those denoted with an asterisk that indicates findings currently reported only in mice in the perinatal to adult and/or adult to aged transitions.