T cells and aging january 2002 update

Abstract

Age-related changes in the immune system may contribute to morbidity and mortality due to decreased resistance to infection and, possibly, certain cancers in the aged. Many studies mostly performed in mice, rats and man but also including monkeys and dogs have established that age-associated immune decline is characterized by decreases in both humoral and cellular responses. The former may be largely a result of the latter, because observed changes both in the B cell germline-encoded repertoire and the age-associated decrease in somatic hypermutation of the B cell antigen receptors are now known to be critically affected by helper T cell aging. As antigen presenting cell (APC) function appears to be well-maintained in the elderly, this review will focus on the T cell. Factors contributing to T cell immunosenescence may include a) altered production of T cell progenitors (stem cell defects, stromal cell defects), b) decreased levels of newly-generated mature T cells (thymic involution), c) aging of resting immune cells, d) disrupted activation pathways in immune cells (stimulation via the T cell receptor for antigen, costimulation, apoptosis control), e) replicative senescence of clonally expanding cells. This review aims to consider the current state of knowledge on the scientific basis for and potential clinical relevance of those factors in immunosenescence in humans. Experiments in other species will be touched upon with the proviso that there are clearly differences between them, especially between humans and rodents, but exactly what those differences are is not completely clear. Given its potential importance and the increasing proportion of elderly people the world over, coupled with the realisation that whereas mortality is decreasing, morbidity may not be decreasing in parallel (1), a better understanding of the causes and impact of immunosenescence may offer the possibility of identifying where prevention or delay of onset, as well as therapeutic intervention, might be beneficial. Amelioration of the effects of dysregulated immune responses in the elderly by replacement therapy, supplementation therapy or other approaches may result in an enhancement of their quality of life, and significant reductions in the cost of medical care in old age.

Impact of CMV and EBV seropositivity on CD8 T lymphocytes in an old population from West-Sicily

“…There was, however, a significant decrease in perforin+ cells, as previously reported (Rukavina et al, 1998). These data are therefore in general agreement with results previously reported in different populations (Pawelec et al, 2002a;Pawelec et al, 2004;Pawelec et al, 2005). In order to examine the general effect of viral infection on T cell subset distribution, we separately analysed these data for young and old individuals, comparing those seropositive for both EBV and CMV with those seronegative.…”

“…shows the surface phenotypes of the CD8 cells in the young and old donors, clearly delineating significantly lower percentages of CD27+, CD28+ and CD45RA+ cells in the elderly, as expected from previous reports (Pawelec et al, 2002a;Pawelec et al, 2004;Pawelec et al, 2005). Reciprocally, the percentage of CD45RO+ cells was significantly increased in the elderly.…”

“…Retrospectively, several years ago oligoclonal expansions of T cells, especially of CD8 cells, had been reported as a characteristic of human and murine ageing (Pawelec et al, 2002a). Later it was established that CMV seropositivity was associated with many of the same phenotypic and functional alterations to T cell immunity as were being reported as biomarkers associated with ageing (Wang et al, 1995;Wedderburn et al, 2001).…”

“…A well-functioning immune system in the elderly is thought to be tightly correlated to health status, and some immunological parameters are often notably reduced especially in the frail elderly (Pawelec et al, 2002a). The OCTO longitudinal study of very elderly Swedes selected for good health at >85 yr of age has shown that a cluster of immunological parameters can be used to predict mortality.…”

Cytokine Serum Profile in a Group of Sicilian Nonagenarians

“…[5] Moreover, in the aging process, and even in centenarians, there is a redistribution of monocytes, neutrophils, B and T subsets, and a quite normal number of T lymphocytes, even if these cells mostly show a memory phenotype, whereas a progressive reduction of virgin cells is observable, which makes the old individuals unable to respond to antigens not previously encountered. [6] Several studies have largely demonstrated an important role of genetic background in the achievement of advanced age. A group of genes that has often been tested for association with successful aging is that which influences inflammation and immune responses.…”