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Review
. 2013 Sep 13:4:271.
doi: 10.3389/fimmu.2013.00271.

Human T cell aging and the impact of persistent viral infections

T Fülöp  1 , A Larbi, G Pawelec
Affiliations
Review

Human T cell aging and the impact of persistent viral infections

T Fülöp et al. Front Immunol. .

Abstract

Aging is associated with a dysregulation of the immune response, loosely termed "immunosenescence." Each part of the immune system is influenced to some extent by the aging process. However, adaptive immunity seems more extensively affected and among all participating cells it is the T cells that are most altered. There is a large body of experimental work devoted to the investigation of age-associated differences in T cell phenotypes and functions in young and old individuals, but few longitudinal studies in humans actually delineating changes at the level of the individual. In most studies, the number and proportion of late-differentiated T cells, especially CD8+ T cells, is reported to be higher in the elderly than in the young. Limited longitudinal studies suggest that accumulation of these cells is a dynamic process and does indeed represent an age-associated change. Accumulations of such late-stage cells may contribute to the enhanced systemic pro-inflammatory milieu commonly seen in older people. We do not know exactly what causes these observed changes, but an understanding of the possible causes is now beginning to emerge. A favored hypothesis is that these events are at least partly due to the effects of the maintenance of essential immune surveillance against persistent viral infections, notably Cytomegalovirus (CMV), which may exhaust the immune system over time. It is still a matter of debate as to whether these changes are compensatory and beneficial or pathological and detrimental to the proper functioning of the immune system and whether they impact longevity. Here, we will review present knowledge of T cell changes with aging and their relation to chronic viral and possibly other persistent infections.

Keywords: CMV; T cells; aging; chronic stimulation; immunosenescence.

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Figures

Figure 1
Figure 1
Phenotypic characterization of T cells and their changes in aging. There are four major differentiation stages of T cells characterized by the presence or absence of different surface markers in this popular model. With aging the naïve cell compartment is shrinking while the memory is expanding. There is also a loss of diversity with aging.
Figure 2
Figure 2
Impact of different chronic viral infections on the immune system and clinical consequences in young and elderly subjects. The immunological and clinical impact of these viral infections is different in young and elderly and even among elderly; however they present a persistent antigenic stimulation throughout life.
Figure 3
Figure 3
Schematic conceptualization of the effects of aging on the immune system. Through the progression of time the immune reserves are decreasing, the baseline is approaching to the threshold for inducing an efficient response, the immune response is less vigorous and maintained due to a complete reshaping of the immune cells by the immune history, such as persistent viral infection, putatively CMV. ↔: Represents possible CMV infection effects on the immune reserve and the threshold.
See this image and copyright information in PMC

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