Impact of aging on T cell repertoire and immunity

Abstract

Immune function declines with age, resulting in increased susceptibility to infection and reduced vaccination efficacy. A major contributing factor to impaired immunity with ageing is age-associated changes in the repertoire of T cells. Specifically, production of naïve T cells declines due to thymic atrophy, and the memory compartment increases progressively with age until it greatly exceeds the naïve compartment. In addition, the memory compartment is further perturbed by the frequent appearance of clonal expansions in the memory CD8 + T cells. As a consequence, the naïve compartment becomes constrained in size, and there is associated loss of repertoire diversity that impacts the ability to respond to new infections and vaccination and can impair previously established memory. A major driving force of clonal expansions in humans is infection with the persistent β-herpesvirus, cytomegalovirus (CMV), with CMV-specific CD8 + T cells progressively dominating the repertoire. In this chapter, we review important advances in our understanding of the impact of age-associated changes in the repertoire on immune function and discuss possible therapeutic approaches to ameliorate All occurrences of "immune senescence" have been changed to "immunosenescence" for consistency. Please check if okay.