Treatment of old mice with IL-2 corrects dysregulated IL-2 and IL-4 production.

Splenic T cells from old BALB/c mice, activated in vitro with antibody to CD3epsilon, secrete more IL-4 but less IL-2 than splenic T cells from young mice. The age-associated increase in IL-4 secretion is associated with a significantly increased concentration of intracellular IL-4 and its mRNA, although there is no increase in the number of activated T cells with intracellular IL-4. In contrast, the age-associated decrease in IL-2 secretion is associated with a significant decrease in the number of activated T cells with intracellular IL-2. In vivo there is a similar age-associated change in the number of activated T cells with detectable cytokine. The number of activated T cells with intracellular IL-4 is comparable in old and young mice, while the number of activated T cells with intracellular IL-2 is significantly decreased in old compared with young mice. Of great interest is the fact that old mice continuously exposed to IL-2 in vivo following the transplantation of J558 cells expressing the transfected IL-2 gene product have an increased number of splenic T cells with intracellular IL-2 that equals the level of such cells observed in young mice. Most important, the effect of continuous IL-2 administration in vivo was stable as spleen cells from old, IL-2-treated mice when stimulated in vitro with anti-CD3epsilon had a young-like pattern of both intracellular IL-2 and IL-4 expression as well as IL-2 and IL-4 secretion following in vitro activation. Thus, it appears that exposure of old mice to exogenous IL-2 can redress the age-associated imbalance in cytokine expression in vivo and cytokine secretion in vitro.