Suppressor of cytokine signaling-1 is a critical regulator of interleukin-7-dependent CD8+ T cell differentiation

Suppressor of cytokine signaling-1 is a critical regulator of interleukin-7-dependent CD8+ T cell differentiation
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DOI:
10.1016/s1074-7613(03)00078-5
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发表时间:
2003-04-01
期刊:
影响因子:
32.4
通讯作者:
Kay, TWH
Kay, TWH
中科院分区:
医学1区
文献类型:
--
作者:
Chong, MMW;Cornish, AL;Kay, TWH

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为了确定 SOCS-1 的组织特异性功能,培养了小鼠,其中个别组织中的 SOCS-1 基因可以被删除。还插入了 SOCS-1 启动子活性的报告基因。使用该报告基因,在胸腺细胞发育的CD4(+)CD8(+)阶段发现SOCS-1高表达。为了研究该表达的功能,在整个胸腺细胞/T/NKT 细胞区室中特意删除了 SOCS-1 基因。与 SOCS-1(-/-) 小鼠不同,这些小鼠没有发生致命的多器官炎症,但出现了多种淋巴异常,包括胸腺细胞向 CD8(+) T 细胞分化增强,以及具有记忆表型 (CD44(hi)CD25(lo)CD69(lo)) 的外周 CD8+ T 细胞比例非常高。发现这些表型与对细胞因子 γ 常见家族的超敏性相关。
To determine the tissue-specific functions of SOCS-1, mice were generated in which the SOCS-1 gene could be deleted in individual tissues. A reporter gene of SOCS-1 promoter activity was also inserted. Using the reporter, high SOCS-1 expression was found at the CD4(+)CD8(+) stage in thymocyte development. To investigate the function of this expression, the SOCS-1 gene was specifically deleted throughout the thymocyte/T/ NKT cell compartment. Unlike SOCS-1(-/-) mice, these mice did not develop lethal multiorgan inflammation but developed multiple lymphoid abnormalities, including enhanced differentiation of thymocytes toward CD8(+) T cells and very high percentages of peripheral CD8+ T cells with a memory phenotype (CD44(hi)CD25(lo)CD69(lo)). These phenotypes were found to correlate with hypersensitivity to the gamma-common family of cytokines.