Age-Associated Changes in Interferon-γ and Interleukin-4 Secretion by Purified Human CD4+ and CD8+ T Cells

Abstract

Aging is associated with a decline in immune function. Interferon-γ (IFN-γ) and interleukin-4 (IL-4), two important immune deviation-related cytokines, are mainly produced by type 1 and type 2 T cells, respectively. To investigate the age-associated changes in the secretion of these two cytokines, 20 elderly and 20 young subjects fulfilling the SENIEUR protocol were enrolled. The ratios of CD4+ to CD8+ T cells were not different between the two age groups. The CD4+ and CD8+ T cells were purified by a magnetic cell sorting system, and then activated by concurrent anti-CD3 and anti-CD28 stimulation. The released cytokines were determined by ELISA. Both the CD4+ and the CD8+ T cells of the elderly individuals secreted a significantly larger amount of IFN-γ after activation. Profound IL-4 production by CD8+ T cells was observed in the older subjects compared with that of the young subjects. These data suggested that age-associated decrease in immunity may be related to an imbalance in the secretion of immune deviation cytokines. The number of IL-4-secreting CD8+ T cells (T cytotoxic 2) rose significantly in the older individuals. Our design also provided a useful way to differentiate the T cell subsets secreting the same cytokine, such as IFN-γ-producing T helper 1 and T cytotoxic 1 cells.

Age-related impairment of human T lymphocytes’ activation: specific differences between CD4+ and CD8+ subsets

“…The role of interferons in aging is not yet clear. Decreased levels of interferons (IFN-a and -g (Miller, 1980;Lio et al, 2000)) were found by some laboratories while other investigators determined increased levels (Fahey et al, 2000;Sakata-Kaneko et al, 2000;Yen et al, 2000). In addition, our data are in concordance with the latter showing that activated T cells of both subsets from elderly individuals produced more IFNg than from young controls.…”

“…Unprimed cells carry the CD45RA isoform of the CD45-receptor, while memory cells express the CD45R0 epitope (Vitetta et al, 1991). We and others (O'Leary et al, 1988;Yen et al, 2000) found no significant changes of the CD4/ CD8 ratio with aging. This is an interesting fact as some neurological disorders (DAT and MS, for instance) show increased CD4/CD8-ratios (Shalit et al, 1995;Crucian et al, 1995b;Schindowski et al, 1999).…”

Th2 Immune Responses and Alternatively Activated Macrophages (AAMacs) in Helminth Infection in Aged Mice

“…Previous studies demonstrated that a helminth infection-induced Th2 immune response is protective in murine models of inflammatory diseases, including inflammatory bowel disease [20] and Type 1 diabetes [15]. Several studies in humans [22,26] Our previous data demonstrated that Th2 cytokine elevation by Hp infection in the small intestine was blocked by anti-CD4 antibody [16]. Therefore, a decrease in the number of CD4 + cells might be one of the reasons for the decline in Th2 cytokine expression in 18 M mice.…”

Alveolar T-helper type-2 immunity in atopic asthma is associated with poor clinical control

“…For these reasons, we believe that variation in ACT score is not reflected by variation in age in the present study. In terms of cytokine profiles in CD4 + T-cells, it has been shown in healthy subjects in three different age groups (21-31 years, 80-81 years and 100-103 years) that the ratio between type-2 cytokines and type-1 cytokines is unaffected by age [43]. Although age-related changes of the immune function in human asthma are yet to be studied in detail, there are studies in animal models and humans suggesting that age can affect both innate and adaptive immune responses [39].…”