Studies on the age-related decline in the response of lymphoid cells to mitogens: measurements of concanavalin A binding and stimulation of calcium and sugar uptake in thymocytes from rats of varying ages.

We have previously demonstrated that mitogenic response of rat thymocytes to concanavalin A (Con A) declines with age (Segal, Troen and Ingbar, Thymus, in press). To elucidate the mechanism underlying this process, we have examined the effect of age on Con A binding and stimulation of calcium and sugar uptake in thymocytes from rats varying in age from 10 to 360 days. Binding of Con A by thymocytes remained unchanged with advancing age. Basal uptake of the glucose analogue 2-[3H]deoxyglucose (2-DG) by rat thymocytes declined with age, becoming significantly lower than maximal values (26 days) at 4 months of age. While the proportionate increase in thymocyte 2-DG uptake produced by Con A remained essentially unchanged. However, because of the decline in basal 2-DG uptake, total uptake of 2-DG in the presence of Con A decreased with age becoming significantly lower than maximal values at 4 months. Basal calcium-45 uptake by thymocytes was practically the same in all the age-groups studied, except at 21 days, where, as with basal 2-DG uptake, it was markedly smaller, But the stimulatory effect of Con A on 45Ca uptake declined progressively with age and was nil at 360 days. From these observations I suggest that the age-related decline in the responsiveness of rat thymocytes to Con A does not result from a change in the binding of Con A by the lymphoid cell, but from, at least in part, a decrease in its cellular stimulation of calcium and sugar uptake.