cAMP regulation of IL-2 receptor expression. Selective modulation of the p75 subunit

As previous experiments have shown that IL-2 activity is abrogated by cAMP, its effect on IL-2R expression by normal and leukemic T lymphocytes was evaluated in detail. The exposure of murine or human T cells to dibutyryl cAMP or the cAMP-elevating drug, forskolin, resulted in a decrease in high affinity IL-2 binding. Equilibrium binding analyses revealed that elevation of cAMP for 4 to 5 h produced a 40 to 50% decrease in the number of detectable receptors, whereas the affinity of the IL-2R interaction remained unchanged. The effect of cAMP could be attributed to a selective effect on the 75-kDa chain of the IL-2R (p75) subunit of the 55-kDa chain of the IL-2R/p75 heterodimer. The mechanism for the decreased expression of high affinity IL-2R appears to be due to a dual effect of cAMP, which functions to both increase the rate of IL-2R internalization, and to decrease the rate of expression of new receptors. Moreover, the effect of cAMP on IL-2 binding to p75 subunits is post-transcriptional, because the steady state levels of p75 mRNA expression are not altered within a time interval that produced nearly a 50% reduction in p75 binding.