Interdependence of cdk2 activation and Interleukin-2R alpha accumulation in T cells

We have shown previously that serum promotes T cell proliferation by acting with T cell receptor (TCR) agonists to efficiently down-regulate p27(Kip1) and activate cdk2-containing complexes. In the studies described here, the effect of serum on the expression of the alpha subunit of the interleukin- 2 receptor (IL-2R alpha) was examined. We found that serum was required for maximal and sustained IL-2R alpha protein expression and consequent IL-2 s ignaling in TCR-activated splenocytes. Serum had no effect on IL-2R alpha m RNA levels and thus modulates IL-2R alpha expression post-transcriptionally . Unlike wild-type splenocytes, splenocytes exhibiting serum-independent cd k2 activation due to loss of p27(Kip1) efficiently expressed IL-2R alpha in serum-deficient medium. Conversely, serum did not promote IL-2R alpha accu mulation in conditions in which cdk2 activity was blocked. These findings d emonstrate that cdk2 activation is necessary and sufficient for IL-2R alpha accumulation in TCR-stimulated splenocytes. On the other hand, IL-2 signal ing was required (at least in part) for cdk2 activation in these cells. Thu s, cdk2 activation, IL-2R alpha expression, and IL-2 signaling are interdep endent events, and we suggest that this feed-forward regulatory loop plays a key role in T cell mitogenesis.