Ligand-induced autoregulation of IL-2 receptor alpha chain expression in murine T cell lines.

The IL-2 receptor (IL-2R) is composed of three chains alpha, beta and gamma. In mice, contrary to the human system, we have previously demonstrated that the IL-2R beta gamma complex does not bind IL-2. Therefore, mouse IL-2 response is completely dependent on the expression of the IL-2R alpha gene product. T cell clones expressing mouse IL-2R beta gamma and the human IL-2R alpha transgene have been studied. When cells are grown in IL-4, mouse IL-2R alpha is not expressed. However, exposure to IL-2 leads to the expression of the endogenous murine IL-2R alpha subunit. The T cell line expressing mouse IL-2R gamma and human IL-2R beta can grow in IL-2 but does not express endogenous murine IL-2R alpha. Transfection of these cells with the human IL-2R alpha gene restores the capacity to induce murine IL-2R alpha. This result demonstrates that IL-2-IL-2R alpha interactions are required for induction of IL-2R alpha. The kinetics of induction and deinduction of murine IL-2R alpha have been studied using clone 18.III. From negative cells, expression of murine IL-2R alpha is a very slow phenomenon. From cells fully expressing IL-2R alpha, deinduction is a two-step process: after a rapid decrease of IL-2R alpha the cells continue to express, for a long period of time, basal levels of murine IL-2R alpha. When cells expressing basal levels of IL-2R alpha are exposed to IL-2, induction of IL-2R alpha is a very rapid phenomenon. The autoregulatory loop formed by IL-2-IL-2R alpha therefore displays different levels of functioning.