...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Tpl2 and ERK transduce antiproliferative T cell receptor signals and inhibit transformation of chronically stimulated T cells
【24h】

Tpl2 and ERK transduce antiproliferative T cell receptor signals and inhibit transformation of chronically stimulated T cells

机译：Tpl2和ERK转导抗增殖T细胞受体信号并抑制长期刺激的T细胞转化

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The protein kinase encoded by the Tpl2 protooncogene plays an obligatory role in the transduction of Toll-like receptor and death receptor signals in macrophages, B cells, mouse embryo fibroblasts, and epithelial cells in culture and promotes inflammatory responses in animals. To address its role in T cell activation, we crossed the T cell receptor (TCR) transgene 2C, which recognizes class I MHC presented peptides, into the Tpl2~(-/-) genetic background. Surprisingly, the TCR2C~(tg/tg)/Tpl2~(-/-) mice developed T cell lymphomas with a latency of 4-6 months. The tumor cells were consistently TCR2C~+CD8~+CD4~-, suggesting that they were derived either from chronically stimulated mature T cells or from immature single positive (ISP) cells. Further studies showed that the population of CD8~+ ISP cells was not expanded in the thymus of TCR2C~(tg/tg)/Tpl2~(-/-) mice, making the latter hypothesis unlikely. Mature peripheral T cells of Tpl2~(-/-) mice were defective in ERK activation and exhibited enhanced proliferation after TCR stimulation. The same cells were defective in the induction of CTLA4, a negative regulator of the T cell response, which is induced by TCR signals via ERK. These findings suggest that Tpl2 functions normally in a feedback loop that switches off the T cell response to TCR stimulation. As a result, Tpl2, a potent oncogene, functions as a tumor suppressor gene in chronically stimulated T cells.
机译：由Tpl2原癌基因编码的蛋白激酶在培养中的巨噬细胞，B细胞，小鼠胚胎成纤维细胞和上皮细胞中Toll样受体和死亡受体信号的转导中起强制性作用，并促进动物的炎症反应。为了解决其在T细胞活化中的作用，我们将识别I类MHC呈递肽的T细胞受体（TCR）转基因2C跨入Tpl2〜（-/-）遗传背景。令人惊讶的是，TCR2C〜（tg / tg）/ Tpl2〜（-/-）小鼠发展为T细胞淋巴瘤，潜伏期为4-6个月。肿瘤细胞始终为TCR2C〜+ CD8〜+ CD4〜-，提示它们来自长期刺激的成熟T细胞或未成熟的单阳性（ISP）细胞。进一步的研究表明，在TCR2C〜（tg / tg）/ Tpl2〜（-/-）小鼠的胸腺中CD8〜+ ISP细胞的种群没有扩大，使得后者的假设不太可能。 Tpl2〜（-/-）小鼠的成熟外周T细胞在ERK激活方面存在缺陷，并在TCR刺激后表现出增强的增殖。相同的细胞在CTLA4的诱导中存在缺陷，CTLA4是T细胞反应的负调节剂，它是由ECR的TCR信号诱导的。这些发现表明，Tp12在反馈回路中正常起作用，该反馈回路关闭了对TCR刺激的T细胞应答。结果，有效的癌基因Tpl2在慢性刺激的T细胞中起着抑癌基因的作用。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号