CD8 T cell clonal expansions & aging: A heterogeneous phenomenon with a common outcome

A highly diverse CD8 T cell repertoire is thought to be critical for maintaining appropriate immune defenses against a variety of pathogens. However, in many aged individuals, the diversity of T cell receptors is significantly reduced by the presence of large, monoclonal expansions of CD8 memory T cells. While ongoing research is focused on understanding the molecular alterations in these expansions, one major hurdle to this goal is the apparent heterogeneity of CD8 clonal expansions, which is apparent even in reductionist systems. In this review, we discuss current evidence that CD8 clonal expansions are a heterogeneous phenomenon, and our evolving understanding of what this heterogeneity tells us about CD8 memory T cell homeostasis and how it is altered in aged individuals.