Effect of rapamycin on the expression of the IL-2 receptor (CD25).
The immunosuppressive macrolide rapamycin inhibits cytokine-driven proliferation of lymphocytes, acting at a later stage of T lymphocyte activation than the related compound FK506 or cyclosporin, which block IL-2 transcription. However, the effect of rapamycin on the expression of the IL-2 receptor alpha-chain (CD25) is less well documented. This study has investigated the effect of rapamycin on mRNA levels of CD25 and membrane expression of IL-2 receptor in human primary T lymphocytes activated by various stimuli. Rapamycin surprisingly inhibits CD25 upregulation subsequent to anti-CD3 or ionomycin stimulation. These effects are not secondary to an IL-2-mediated CD25 up-regulation, as rapamycin inhibits neither IL-2 synthesis nor IL-2-induced CD25 mRNA. Interestingly, 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 inhibition of T cell activation may involve not only IL-2-driven proliferation, but also suppression of CD25 up-regulation.
Woerly
G
G
Institute of Pathology, University of Basel, Switzerland.
Brooks
N
N
Ryffel
B
B
D002478:Cells, Cultured; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D011090:Polyenes / Q000494:pharmacology*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D020123:Sirolimus; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D007166:Immunosuppressive Agents; D007376:Interleukin-2; D011090:Polyenes; D015375:Receptors, Interleukin-2; D020123:Sirolimus