Beneficial and detrimental manifestations of age on CD8+ T-cell memory to respiratory pathogens

Abstract

Increasing age is associated with a decline in adaptive immunity and poorer responses to vaccination. While specific immune defects have clearly been defined in the naïve T-cell pool of aged individuals, much less is known about the memory T-cell pool. Current data suggest that T-cell memory generated in an aged individual has a reduced capacity to mediate recall responses due primarily to defects in the proliferative capacity of individual cells. These defective recall responses in the aged can be further compounded by the development of 'holes' in the T-cell repertoire due to a dwindling supply of naïve T-cell precursors. In contrast, T-cell memory generated in young individuals undergoes a variety of changes over time including both an increase in the proliferative capacity of individual memory T-cells and a decrease in the overall efficacy of the recall response in the lung. Furthermore, the development of T-cell clonal expansions with age can have a dramatic impact on the makeup of the memory T-cell pool, thereby influencing the number of pathogenspecific T-cells capable of participating in the recall response. Collectively, these changes appear to reflect the redistribution of memory T-cell subsets within the memory T-cell pool and the dysregulation of memory T-cell homeostasis over time. This review outlines each of these processes and discusses their implications for vaccination in the elderly.