Human memory T cells: generation, compartmentalization and homeostasis

Abstract

Most of our understanding of memory T cell generation, function and maintenance comes from mouse studies, which cannot recapitulate the exposure to diverse antigens and microbiota that occurs over many decades in humans. Memory T cell frequency dynamically changes throughout the human lifetime and this can be divided into three phases: memory generation, memory homeostasis and immunosenescence. CD45RO⁺CD45RA⁻ T cells comprise diverse memory T cell subsets, including central memory T (T_CM) cells, effector memory T (T_EM) cells, stem cell memory T (T_SCM) cells and tissue-resident memory T (T_RM) cells, which are heterogeneous in their generation, distribution and function. Memory T cells that are specific for antigens from ubiquitous pathogens and possibly from endogenous flora are generated early in life and are preferentially compartmentalized at the sites of infection throughout adulthood. Human memory T cells in diverse tissue sites are homeostatically maintained, potentially through tonic T cell receptor signalling, and can show extensive cross reactivity and can persist for decades. The induction of memory CD4⁺ and CD8⁺ T cells through vaccination can enhance protection against pathogens, and might be improved by considering the anatomical location and the timing of vaccine administration during the early stages of life.