Increased Neopterin Concentration in Older Age Coincides with Decline of CD28+CD45RA+ T-cells

Abstract

Abstract Neopterin is produced from human monocyte-derived macrophages and dendritic cells upon Stimulation with interferon-y, 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 agedependency 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: rs = -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 (r+ = -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.