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.
Demaison
C
C
Unité d'Immunogénétique Cellulaire, Institut Pasteur, Paris, France.
Chastagner
P
P
Moreau
J L
JL
Thèze
J
J
D000818:Animals; D015152:Blotting, Northern; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis* / Q000187:drug effects* / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*; D014162:Transfection / Q000235:genetics
D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D015847:Interleukin-4