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

被引:19
作者
Demaison, C [1 ]
Chastagner, P [1 ]
Moreau, JL [1 ]
Theze, J [1 ]
机构
[1] INST PASTEUR,UNITE IMMUNOGENET CELLULAIRE,F-75015 PARIS,FRANCE
关键词
activation; cytokine responsiveness; IL-2; IL-2 receptor alpha; beta and gamma chains; proliferation; T cell;
D O I
10.1093/intimm/8.10.1521
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:1521 / 1528
页数:8
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