Cyclosporin A inhibits the interleukin 2 receptor α chain gene transcription but not its cell surface expression: the α chain stability can explain this discrepancy

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Abstract
The effect of the immunosuppressor cyclosporin A (CsA) on the expression of interleukin (IL) 2 receptors was investigated in a human T cell line IARC301 which constitutively expresses such receptors. This cell line also spontaneously secretes IL 2 which supports its autocrine growth. We have previously shown that CsA prevents the constitutive transcription of the IL 2 gene in these cells. Here we show that as soon as 4 h after CsA addition, the transcription of the gene encoding the α chain (p55) of IL 2R was inhibited. IL 2 can transiently increase the expression of this gene. CsA did not prevent this transient IL 2‐dependent induction of IL 2Rα, but could still partially inhibit it. Once IL 2 induction was over, CsA exerted its full inhibition. Thus, CsA does not seem to inhibit IL 2Rα gene transcription simply by inhibition of IL 2 synthesis. However, no modification of IL 2Rα expression on the cell surface could be detected after 48 h in the presence of CsA. This discrepancy between the effect of CsA on IL 2Rα expression as probed at the mRNA or the protein level can be accounted for by the stability of the IL 2Rα protein after synthesis. Indeed, the half‐life of IL 2Rα chain is longer than 40 h. This suggests that the α chain, after it is endocytosed together with the β chain as a component of high‐affinity IL 2R, might recycle back to the cell surface.