Changes in Lymphocyte Subsets, Interleukin 2, and Soluble Interleukin 2 Receptor in Old and Very Old Age

Abstract

In this study, the changes in some of the cellular components of the immune system and the activity of the cytokine interleukin 2, important for immune activation and lymphocyte proliferation, were measured in a large cross-sectional study of all age groups including octogenarian and nonagenarian subjects. In 206 apparently well community-living subjects, the absolute lymphocyte count and T and B cell numbers fell a little in old and very old subjects. Within the T cell compartment, helper/inducer CD4+ T cells, together with their subsets identified as ‘naive’ (CD4+/CD45RA+) and ‘memory’ (CD4+/CD45RO+) cells, also showed a decline with increased age. The suppressor/cytotoxic CD8+ subset showed no age-related change. The levels of the cytokine interleukin 2 were very low in octogenarian and nonagenarian subjects, while the soluble interleukin 2 receptor levels increased with increasing age. The interleukin 2 levels were associated with number and percentage of the ‘memory’ (CD4+/CD45RO+) subset of T cells which mediates the host response to previously met antigens. Since the interleukin 2 values were very low in the oldest groups and were associated with a reduced ‘memory’ (CD4+/CD45RO+) compartment, this suggests a possible mechanism of why the very elderly subject is more susceptible to morbidity and mortality from infectious or other agents.

Cytomegalovirus Seropositivity Drives the CD8 T Cell Repertoire Toward Greater Clonality in Healthy Elderly Individuals

“…It would be of great interest to determine the CD4 response against CMV in our elderly population. Indeed, absolute CD4 counts do diminish with aging, and CD4 hyporesponsiveness is well documented in such individuals (45). We have also observed that CMV-specific T cells are uniformly bcl-2 ϩ , indicating resistance to apoptosis, which is reminiscent of cells that have reached replicative senescence in cell culture (46).…”

Linkage analysis of variations in CD4:CD8 T cell subsets between C57BL/6 and DBA/2

“…Flow cytometry was then used to determine the ratio of the numbers of ␣␤TCR + T cells bearing CD4 to those bearing CD8. Since CD4:CD8 ratio varies with age, [1][2][3][4] the ratios in these mice were all measured between 4 to 8 weeks of age. The CD4:CD8 ratios for B6, DBA/2, (B6 × DBA.2)F1, (B6 × DBA/2)F2, and (B6 × DBA/2)F1 × DBA/2 testcrosses are presented for lymph node T cells in Figure 1a.…”

“…For example, the CD4:CD8 ratio falls as animals age. [1][2][3][4] Infection, particularly with viruses, tends to increase disproportionately the numbers of mature T cells bearing CD8. [5][6][7][8] Autoimmunity, diet and even exposure to sunshine have been reported to affect the ratio.…”

Herpesvirus-Specific CD8 T Cell Immunity in Old Age: Cytomegalovirus Impairs the Response to a Coresident EBV Infection

“…The human immune system shows a functional decline during aging with major alterations such as thymic involution, changes in lymphocyte counts, impaired responses to mitogens and Ags in vitro, clonal expansions, and immune senescence (12,24,25). One characteristic of immune senescence is an accumulation of CD28 Ϫ…”