Increased neopterin concentration in older age coincides with decline of CD28+CD45RA+ T-cells

Abstract

Neopterin is produced from human monocyte-derived macrophages and dendritic cells upon stimulation with interferon-γ, and increased neopterin concentrations thus indicate cell-mediated immune activation. In healthy individuals increasing neopterin concentrations are found with increasing age, which is also evident from the age-dependency of reference values of serum neopterin concentrations. Increase of neopterin concentrations in the elderly may relate to, e.g., altered T lymphocyte differentiation with age. In this study, serum neopterin concentrations of 138 persons (median age: 34 years; interquartile range 29.0 - 67.8 years) were investigated and compared to age and to the percentage of CD28+CD45RA+ or CD28 +CD45RO+ subsets among CD8+ T cells. With increasing age, the percentage of CD28+CD45RA+ in CD8 + T-cells decreased (Spearman's rank correlation coefficient: r s = -0.561; p < 0.0001) accompanied by an increase of the percentage of CD28+CD45RO+ in CD8+ T-cells (rs = +0.221; p < 0.01). Serum neopterin concentrations increased with age (rs = +0.541; p < 0.0001). This increase of neopterin concentration was accompanied by a decreased percentage of CD28 +CD45RA+ in CD8+ T-cells (rs = -0.287; p < 0.001). Multivariate analyses revealed that the inverse relationship between the percentage of CD28+CD45RA+ in CD8+ T-cells and neopterin concentrations was at least partly independent from age. Thus, investigation allows to conclude that an increase of neopterin concentrations with older age is accompanied by a loss of naive CD28+CD45RA+ CD8+ T-cells. Data suggest that the subset of CD28-CD8+ T cells, which is developing in states of sustained immune activation, is important for a chronic production of interferon-γ which in turn gives rise to increased neopterin concentrations.