ALTERED ANTIGEN RECEPTOR SIGNALING IN ANERGIC T-CELLS FROM SELF-TOLERANT T-CELL RECEPTOR BETA-CHAIN TRANSGENIC MICE

ALTERED ANTIGEN RECEPTOR SIGNALING IN ANERGIC T-CELLS FROM SELF-TOLERANT T-CELL RECEPTOR BETA-CHAIN TRANSGENIC MICE
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DOI:
10.1073/pnas.88.15.6682
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发表时间:
1991-08-01
影响因子:
11.1
通讯作者:
MARRACK, P
MARRACK, P
中科院分区:
综合性期刊1区
文献类型:
--
作者:
BLACKMAN, MA;EINKEL, TH;MARRACK, P

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在T细胞受体(TcR)V-β-8.1转基因小鼠系中,T细胞对次要淋巴细胞刺激抗原Mls-1a的耐受性通过克隆缺失和克隆无反应性来维持。从这些小鼠中分离的约20-50%的外周CD 4+(而不是CD 8+)T细胞是无反应性的,并且在TcR连接后不能增殖。我们研究了从这些小鼠中分离的外周T细胞中T细胞信号传导的关键事件。在这份报告中,我们表明,无能的CD 4 + T细胞不动员钙或表达受体白细胞介素2(IL-2)TcR结扎后。然而,细胞保留活力和功能潜力,因为佛波醇12-肉豆蔻酸酯13-乙酸酯和离子霉素的刺激绕过受体介导的信号传导的阻断,并诱导IL-2受体表达和无反应性细胞的增殖。
T-cell tolerance to the minor lymphocyte-stimulating antigen Mls-1a in a T-cell receptor (TcR) V-beta-8.1 transgenic line of mice is maintained by both clonal deletion and clonal anergy. Approximately 20-50% of peripheral CD4+ (but not CD8+) T cells isolated from these mice are anergic and fail to proliferate following TcR ligation. We have examined key events in T-cell signaling in peripheral T cells isolated from these mice. In this report, we show that the anergic CD4+ T cells did not mobilize calcium or express receptors for interleukin 2 (IL-2) following TcR ligation. However, the cells retained viability and functional potential because stimulation with phorbol 12-myristate 13-acetate and ionomycin bypassed the block in receptor-mediated signaling and induced IL-2 receptor expression and proliferation of the anergic cells.