LIGAND-INDUCED AUTOREGULATION OF IL-2 RECEPTOR-ALPHA CHAIN EXPRESSIONIN 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 demon strated that the IL-2R beta gamma complex does not bind IL-2, Therefor e, mouse IL-2 response is completely dependent on the expression of th e 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 cell s are grown in IL-4, mouse IL-2R alpha is not expressed, However, expo sure to IL-2 leads to the expression of the endogenous murine IL-2R al pha 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 re stores the capacity to induce murine IL-2R alpha, This result demonstr ates 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, expr ession of murine IL-2R alpha is a very slow phenomenon, From cells ful ly 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 lon g period of time, basal levels of murine IL-2R alpha, When cells expre ssing 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 b y IL-2-IL-2R alpha therefore displays different levels of functioning.