Age-related changes in the expression of IL-2 and high-affinity IL-2 binding sites

T cell responsiveness to in vitro stimulation is severely diminished in the aged. Recent studies would suggest that this may be due, at least in part, to a reduction in interleukin 2 (IL-2) secretion and high-affinity IL-2 receptor (HA-IL-2R) expression. In this report we confirm and extend these studies to show that the fall in IL-2 production is not due to reduced numbers of IL-2 mRNA producing T cells but rather to a decline in the relative amount of IL-2 mRNA expressed per cell. Although we found an age-related reduction in the number of high-affinity binding sites on phytohaemagglutinin-activated T cell blasts by ligand-binding studies, we did not observe alterations in the number of cells that expressed both chains of the HA-IL-2R by two-colour immunofluorescence using monoclonal antibodies specific for p55 (alpha) chain and p75 (beta) chain. However, we did observe a substantial diminution in the number of activated T cells expressing p55 alone in the aged. Given that IL-2 upregulates p55 expression and is involved in the formation of HA-IL-2R, our results suggest that defective IL-2 expression is the primary lesion in age-related T cell senescence.