Monocyte-mediated regulation of cellular immunity in humans: loss of suppressor activity with ageing

The effect of ageing on cellular immunity in humans was investigated. Human T cell cytotoxicity (CMC) measured by an in vitro xenogeneic assay was found previously to be depressed in individuals greater than 60 years old (group 2) compared to individuals less than 50 years old (group 1). Removal of plastic-adherent cells prior to sensitization in the xenogeneic CMC assay of human peripheral blood mononuclear cells (HPBM) resulted in a significantly higher rise (P less than 0.001, Wilcoxon rank test) in CMC activity in group 1 compared to group 2. Replacement of plastic-adherent cells (greater than 35% monocytes) to HPBM depleted of monocytes returned the CMC activity to the level observed with unseparated HPBM. Separation of HPBM on Percoll density gradients into monocyte-enriched (less than 75%) and monocyte-depleted (less than 3%) fractions indicated that monocytes were responsible for suppressing CMC in group 1. These results are consistent with the hypothesis that monocyte suppressor function for CMC response declines in ageing humans. When indomethacin (1 microgram/ml) was added to HPBM the Con A- and PHA-induced DNA synthetic response rose in groups 1 and 2. Indomethacin induced a significantly larger (P less than 0.01) rise in suboptimal PHA mitogenesis in group 1 compared to group 2. Individuals whose CMC response rose following adherent cell depletion were examined for the effect of indomethacin on the CMC response of their HPBM. In nine of 13 cases, addition of indomethacin also resulted in increased CMC activity.