Figure 1.

Changes to the T cell pool during aging reflect differences in subset proportions as well as age-related changes to individual T cells. A) The proportional representation of T cell subsets depends on regulatory molecule expression, the infection history of the individual, current infections and stochastic events. T cell survival may be enhanced by TCR cross-reactivity, which would increase TCR stimulation and thus increase positive signaling. T cell location may also influence survival based on access to cytokines, contact with APCs, CD4⁺ T cell help or inflammatory signals. Finally, access to positive and negative signals both in terms of ligand accessibility and the expression of regulatory receptors on the T cell surface is likely to shape the development of the memory pool and select for certain T cell clones. B) During the course of aging, individuals are exposed to infection, and antigen-specific T cells form a memory population (orange) which comes to dominate the T cell pool. Common, chronic latent infections such as CMV induce the development of senescent cells (green). C) Individual-specific exposure to infection, for example to chronic active infections, can alter the proportion of T cell subsets in the total T cell pool. The resultant memory pool is very heterogeneous, involving the accumulation of memory cells, senescent cells, exhausted cells (blue) and aged naïve cells (purple) following acute, latent chronic and active chronic infection, and homeostatic proliferation.

APC: antigen-presenting cell; TCR: T cell receptor