EFFECT OF RAPAMYCIN ON THE EXPRESSION OF THE IL-2 RECEPTOR (CD25)

The immunosuppressive macrolide rapamycin inhibits cytokine-driven pro liferation of lymphocytes, acting at a later stage of T lymphocyte act ivation than the related compound FK506 or cyclosporin, which block IL -2 transcription. However, the effect of rapamycin on the expression o f the IL-2 receptor alpha-chain (CD25) is less well documented. This s tudy has investigated the effect of rapamycin on mRNA levels of CD25 a nd membrane expression of IL-2 receptor in human primary T lymphocytes activated by various stimuli. Rapamycin surprisingly inhibits CD25 up regulation subsequent to anti-CD3 or ionomycin stimulation. These effe cts are not secondary to an IL-2-mediated CD25 up-regulation, as rapam ycin inhibits neither IL-2 synthesis nor IL-2-induced CD25 mRNA. Inter estingly, sensitivity to rapamycin correlates with the requirement of de novo protein synthesis, as demonstrated by anisomycin inhibition of both ionomycin- and CD3-induced CD25 transcription. Thus, rapamycin i nhibition of T cell activation may involve not only IL-2-driven prolif eration, but also suppression of CD25 up-regulation.