Changes of T Cell Receptor (TCR) αβ Repertoire in the Face of Aging and Persistent Infections

Abstract

Aging is associated with profound dysfunction in T cell responses, leading to increased susceptibility to infection. One potential factor underlying this susceptibility is the decrease in output of new naïve TCRαβ T cells from the aging thymus that, coupled to reduced peripheral T cell maintenance later in life, leads to a decline in αβ T lymphocyte numbers with aging (Note that much less is known about maintenance and importance of diversity within the TCRγδ and other specialized, TCR-restricted populations of T cells, which are not the topic of this chapter). In mouse studies where experimental T cell tracking is possible, the maintenance of naive T cells over a lifespan was found to be asymmetrical – some clonotypes were found to have a competitive survival advantage over others. However, the clonotypes that survived into old age did not necessarily provide the best protection against infectious challenge. Understanding how aging impacts both the naïve and primed/elicited T cell repertoires, and how naïve T cells are maintained over the lifespan remains a critical challenge to understanding the decline of T cell immunity with aging.

Here we review what is currently known about the mechanisms that generate and maintain TCRαβ repertoire diversity, and how TCR repertoires change over the lifespan. We hope to emphasize gaps in our understanding of T cell immunity, specifically when considered in the context of the diverse microbial environment that we experience over a lifetime.