Age-related changes in immunity: implications for vaccination in the elderly.

Average life expectancy is continuously rising in all developed countries, leading to an ever-increasing elderly population. Of the many functions of the body affected by the complex process of ageing, the immune system in particular undergoes various changes, collectively termed immunosenescence. As a result, elderly people are more susceptible to infections and are frequently less protected by vaccines. This review summarises the effect of ageing on immunity, emphasising the age-associated changes within T and B cells at a molecular and cellular level. Furthermore, it discusses strategies, such as the addition of immunostimulatory adjuvants and the use of potent antigen-delivery systems, that may counteract age-related defects in immune responses to vaccination. A proper understanding of how immunological memory is affected by ageing, and the introduction of strategies to ameliorate vaccine efficacy in the elderly, might reduce the incidence and the severity of infectious disease within this fragile age group and have a strong impact on the quality of life of elderly individuals.

Age-associated changes within CD4+ T cells.

As individuals age their ability to respond and clear pathogens declines, leading to a greater incidence and severity of infectious diseases. Additionally, the efficacy of vaccines is frequently decreased in elderly persons. Increased susceptibility to infections and reduced protection after vaccination reflect the impact of age-related changes on the immune system. The immune system undergoes a wide range of changes with increasing age. The aim of this review is to summarize cellular and molecular aspects of aging CD4(+) T cells. CD4(+) T cells play an essential role in mediating both humoral and cellular immune responses. Therefore, age-associated dysfunctions within CD4(+) T cells have a strong clinical impact. Improving our understanding of the aged CD4(+) T cells, in particular but also of the aged immune system in general, is crucial for developing effective prevention and treatment programs which will facilitate healthy aging and improve the quality of life of the elderly population.

Naive T cells in the elderly: are they still there?

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.

Age-related differences in phenotype and function of CD4+ T cells are due to a phenotypic shift from naive to memory effector CD4+ T cells.

Based on the combined expression of CD27 and CD28, a putative model of T cell differentiation has been previously proposed. We used CD27 and CD28 expression in order to comparatively study the size, cytokine production capacity and proliferative response of CD4+ T cell sub-populations from healthy young and elderly volunteers. Elderly persons had a lower percentage of CD27+CD28+ but a higher percentage of CD27-CD28+ and CD27-CD28-CD4+ T cells than the young persons. CD27-CD28-CD4+ T cells were present, although at relatively low numbers, in the vast majority of the healthy elderly donors but were only sporadically detected in young persons. Each CD4+ T cell sub-population exhibited a distinct phenotype and cytokine production profile, which were not affected by age. When purified CD27+CD28+ were stimulated by staphylococcal enterotoxin B, they proliferated to a greater extent than CD27-CD28+ and CD27-CD28-CD4+ T cells. However, we did not observe age-related differences in proliferative response of each sub-population. We concluded that although the size of the different sub-populations differed between the young and the old group, the functional characteristics of each sub-population were the same in both age groups. This suggests that on a per cell basis there is no functional impairment of CD4 memory T cells in elderly persons. Consequently, potential differences in the function of the total CD4+ T cell population are most likely due to different composition of repertoire.