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 CD3 epsilon, secrete more IL-4 but less IL-2 than splenic T cells from young mice. The age-associated increase in IL-4 secretion is asso ciated with a significantly increased concentration of intracellular I L-4 and its mRNA, although there is no increase in the number of activ ated T cells with intracellular IL-4. In contrast, the age-associated decrease in IL-2 secretion is associated with a significant decrease i n the number of activated T cells with intracellular IL-2. In vivo the re is a similar age-associated change in the number of activated T cel ls with detectable cytokine. The number of activated T cells with intr acellular IL-4 is comparable in old and young mice, while the number o f activated T cells with intracellular IL-2 is significantly decreased in old compared with young mice. Of great interest is the fact that o ld mice continuously exposed to IL-2 in vivo following the transplanta tion of J558 cells expressing the transfected IL-2 gene product have a n increased number of splenic T cells with intracellular IL-2 that equ als the level of such cells observed in young mice. Most important, th e effect of continuous IL-2 administration in vivo was stable as splee n cells from old, IL-2-treated mice when stimulated in vitro with anti -CD3 epsilon had a young-like pattern of both intracellular IL-2 and I L-4 expression as well as IL-2 and IL-4 secretion following in vitro a ctivation. Thus, it appears that exposure of old mice to exogenous IL- 2 can redress the age-associated imbalance in cytokine expression in v ivo and cytokine secretion in vitro.