THE SENSITIVITY OF IL-4 PRODUCTION FOR CAMP INDUCERS IS LOST IN CD4-CELLS FROM AGED MICE( T)

CD4+ T cell clones have been demonstrated to display a differential se nsitivity for the induction of cAMP. In the present study we investiga ted whether the differential sensitivity of CD4+ T cell clones tor cAM P inducers is also applicable to freshly isolated phenotypically and f unctionally distinct CD4+ T cell subsets that develop naturally in agi ng mice. Our results show that the concanavalin A induced and anti-CD3 induced proliferative response of CD4+ T cells from young mice is mor e sensitive for prostaglandin E2 (PGE2) and forskolin than that of the ir aged counterparts, although the IL-2 production by these cells was equally sensitive. In contrast, only a slight or no inhibitory effect of these cAMP inducers was found when the cells were stimulated with t he combination of phorbol myristate acetate and ionomycin. In contrast to the findings obtained with Th2 clones, IL-4 production by freshly isolated CD4+ T cells was inhibited by the cAMP inducers, whereas exog enous IL-2 had no restorative effect. However, the IL-4 production by CD4+ T cells from aged mice was less sensitive than the IL-4 productio n by CD4+ T cells from young mice, although CD4+ T cells from aged mic e showed significantly higher levels of intracellular cAMP in response to PGE2. These higher levels of cAMP were related to the increased fr action of memory cells in aged mice: the Mel-14- Pgp-1++ CD4+ T cells responded with at least 2-fold higher levels of intracellular cAMP tha n the naive cells in young as well as in aged mice. Although memory CD 4+ T cells from young as well as aged mice responded vigorously to PGE 2 by an enhancement of intracellular cAMP, only the IL-4 production by cells from young mice was significantly inhibited. Therefore, it is n ot likely that the induction of cAMP is a major event in the skewing o f a primary response towards a Th2 type of response.