Naïve T Cells in the Elderly

Abstract

One of the most striking changes in the primary lymphoid organs during human aging is the progressive involution of the thymus. As a consequence, the rate of naïve T cell output dramatically declines with age and the peripheral T cell pool shrinks. These changes lead to increased incidence of severe infections and decreased protective effect of vaccinations in the elderly. Little is, however, known of the composition and function of the residual naïve T cell repertoire in elderly persons. To evaluate the impact of aging on the naïve T cell pool, we investigated the quantity, phenotype, function, composition, and senescence status of CD45RA(+)CD28(+) human T cells--a phenotype generally considered as naïve cells--from both young and old healthy donors. We found a significant decrease in the number of CD45RA(+)CD28(+) T cells in the elderly, whereas the proliferative response of these cells is still unimpaired. In addition to their reduced number, CD45RA(+)CD28(+) T cells from old donors display significantly shorter telomeres and have a restricted TCR repertoire in nearly all 24 Vbeta families. These findings let us conclude that naïve T cells cannot be classified with conventional markers in old age.

H1 histone subtype constitution and phosphorylation state of the ageing cell system of human peripheral blood lymphocytes

“…However naïve T cells also enter a state of senescence due to their extended replicative history so as to maintain the homeostasis of the naïve compartment during ageing (Nikolich-Zugich, 2005;Goronzy et al, 2007). Moreover, there are numerous studies that have shown that telomere shortening occurs in both naïve (Pfister et al, 2006) and…”

“…It is known that both CD4 and CD8 cell populations change during ageing. The major characteristic of this immune ageing process is the decrease in the number of naïve T cells with age (Goronzy et al, 2007;Pfister et al, 2006;Kovaiou et al, 2005). The repeated stimulation of memory cells leads to their replicative exhaustion and senescence.…”

Nutrition, diet and immunosenescence

“…Whit these changes in CD8 + T cell functionality, aged people are more vulnerable to viral infections (Webster, 2000). Naïve CD4 + T cell function in the aged decreases due to the accumulation of intrinsic and extrinsic defects, effectively limiting effective antibody responses (Pfister et al, 2006). The TCR signalling cascade shows age-related modifications as in the case of JAK/STAT pathway (Fulop et al, 2006) and the lipid raft polarization that affects IL-2 and IL-6 receptor signalling in T cells.…”

A virosomal formulated Her-2/neu multi-peptide vaccine induces Her-2/neu-specific immune responses in patients with metastatic breast cancer: a phase I study

“…T cells, no significant differences in the distribution of lymphocyte subpopulations (CD4, CD45RO, CD8, CD19) were detected between the tumor patients and the healthy controls before and after vaccination. Also the percentage of CD4 T cells expressing CD62L, a homing receptor on naïve T cells, did not significantly differ between the two groups and declined after vaccination, most probably as a result of immune responsiveness to the vaccine antigens, as also described for other vaccines in healthy adults [13,29].…”