Interleukin-2 receptor (CD25) upregulation on human T-lymphocytes: sensitivity to immunosuppressants is defined by the mode of T-lymphocyte activation.
We investigated the transcription and expression of the interleukin-2 receptor (IL-2R, CD25) in human T-lymphocytes after different modes of T-lymphocyte stimulation in the presence of the immunosuppressants cyclosporin (CsA) and tacrolimus (FK506) as well as the structurally related macrolide rapamycin. We demonstrate that CsA and FK506 inhibited IL-2R (CD25) gene transcription and protein expression after stimulation by anti-CD3 or ionomycin, but not by phorbol ester or IL-2. Rapamycin, which does not affect IL-2 transcription, surprisingly inhibited IL-2R upregulation after anti-CD3- or ionomycin-induced stimulation, but not by phorbol ester or IL-2. Interestingly, the protein synthesis inhibitor anisomycin inhibited anti-CD3- or ionomycin-, but not phorbol ester- and IL-2-induced CD25 gene transcription indicating the dependence on de novo protein synthesis of the former pathways. These data suggest that the pharmacological effect of the imunosuppressants tested on IL-2R gene expression may be predicted by the requirement of protein synthesis of a given activation pathway.
Ryffel
B
B
Institute of Toxicology, University of Zürich, Schwerzenbach, Switzerland.
Willcocks
J L
JL
Brooks
N
N
Woerly
G
G
D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; 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 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D020123:Sirolimus; D013601:T-Lymphocytes / Q000737:chemistry / Q000187:drug effects* / Q000276:immunology; D016559:Tacrolimus / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
D007166:Immunosuppressive Agents; D007376:Interleukin-2; D011090:Polyenes; D015375:Receptors, Interleukin-2; D016572:Cyclosporine; D013755:Tetradecanoylphorbol Acetate; D020123:Sirolimus; D016559:Tacrolimus