Immune function declines as we age resulting in an increased susceptibility to new infections and re-activation of latent pathogens to which we were once immune [1,2]. Paradoxically, this dampened immune responsiveness observed during immune

S.M. Henson (H)

Centre for Microvascular Research, William Harvey Research Institute, Barts & The London School of Medicine and Dentistry, Queen Mary, University of London,

Charterhouse Square, London EC1M 6BQ, UK e-mail: This email address is being protected from spam bots, you need Javascript enabled to view it

© Springer International Publishing Switzerland 2017 V. Bueno et al. (eds.), The Ageing Immune System and Health, DOI 10.1007/978-3-319-43365-3_2

ageing is also associated with a low-grade chronic inflammation, termed ‘inflammageing’ [3,4]. Although inflammation is critical for dealing with infections and tissue damage, inflammageing appears to be physiologically deleterious and predictive of all-cause mortality in multiple aged cohorts [5]. Immune senescence results from defects in different leukocyte populations, however the dysfunction is most profound in T cells [6, 7]. The responses of T cells from aged individuals are typically slower and of a lower magnitude than those of young individuals, whether the response is measured by proliferation [8], telomerase activity [8] or the induction of signalling events [9]. The T cell pool contains a number of functionally distinct subsets: CD4+ T cells, CD8+ T cells, and regulatory T cells together with nonconventional T cells, while not all equally affected by age, the overall T cell number does decline dramatically as a result of thymic atrophy [10,11]. This reduced thymic output leads to the homeostatic expansion of peripheral T cells to regenerate the T cell pool, which together with the turnover of T cells in response to repeated antigenic stimulation eventually lead to the accumulation of oligoclonally expanded, functionally impaired T cells [1, 12]. Recent evidence suggests that the rise in homeostatic expansion during ageing may also be responsible for the abundance of memory- phenotype T cells specific for viral antigens in adults never previously infected [13]. Whatever the cause of these age-related changes to the T cell compartment, they all contribute to the inability of the aged immune system to respond to new antigenic challenge and mount effective responses following vaccination [14].

This chapter will examine how T cell memory is affected during ageing, the contribution of changes to the T cells themselves, as well as the consequence of an altered regulatory balance will be discussed, and will show how the generation of highly differentiated end-stage T cells contributes to age-associated disease.

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