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 reduced immune responses. For example, aging is associated with poor vaccine responses to pulmonary pathogens such as influenza virus. 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. Accumulating 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. However, it is possible that this deficit in naïve T cell repertoire is at least partly made up by “virtual memory” cells, which accumulate with age and can mediate protective immunity. 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 pathogen-specific 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 chapter outlines each of these processes and discusses their implications for vaccination against respiratory pathogens in the elderly.