Intermediate- and high-affinity interleukin-2 receptors expressed in an IL-4-dependent T-cell line induce different signals.
In order to understand the respective roles of IL-2R alpha and IL-2R beta subunits in transmission of the interleukin-2 (IL-2)-mediated growth signals, we have established two IL-4-dependent murine T-cell clones stably expressing the human IL-2R beta chain and three clones stably expressing the human IL-2R alpha chain. Whereas parental LD8 cells (which express only the murine IL-2R beta chain) do not proliferate in response to IL-2, cell lines stably expressing human IL-2R beta or the chimeric IL-2R alpha beta complex proliferate in response to IL-2. Stably transfected cells expressing the chimeric high-affinity receptor (human IL-2R alpha and murine IL-2R beta) expressed de novo endogenous murine IL-2R alpha when cultured in the presence of IL-2 but not IL-4. Both chimeric and endogenous receptors are functional in response to IL-2, since only addition of both anti-human and anti-murine IL-2R alpha monoclonal antibodies (mAb) inhibited IL-2-induced proliferation. Taken together, our results strongly suggest that human and murine IL-2R beta molecules are different since interaction of IL-2 with human p70 IL-2R is sufficient for transduction of proliferative signals in the absence of p55 IL-2R or, alternatively, that over-expression of the IL-2R beta chain renders cells responsive to IL-2. In addition, IL-2 stimulation of T cells through different forms of IL-2R results in the induction of distinct cellular responses.
Rebollo
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Centro de Investigaciones Biológicas, Madrid, Spain.
Silva
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D015152:Blotting, Northern; D002455:Cell Division / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000032:analysis* / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
D007376:Interleukin-2; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D015847:Interleukin-4; D004247:DNA