NORMAL PERIPHERAL T-CELL FUNCTION IN C-FOS-DEFICIENT MICE
NORMAL PERIPHERAL T-CELL FUNCTION IN C-FOS-DEFICIENT MICE
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DOI：
10.1128/mcb.14.3.1566
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发表时间：
1994-03-01
影响因子：
5.3
通讯作者：
RAO, A
中科院分区：
文献类型：
--
作者：
JAIN, JN;NALEFSKI, EA;RAO, A
普遍存在的转录因子Fos和Jun在通过T细胞抗原受体刺激的T细胞中被快速诱导，并调节活化的T细胞中细胞因子（包括白介素2）的转录。由于T细胞发育过程中胸腺细胞的阳性和阴性选择也依赖于T细胞受体的活化，因此Fos和Jun也可能在胸腺细胞发育中发挥作用。Fos和Jun作用于白细胞介素2启动子中的几个调控元件，包括AP-1和NFAT位点。使用抗血清特异性个别Fos和Jun家族成员，我们表明，c-Fos以及其他Fos家族成员存在于诱导型AP-1和NFAT复合物的活化小鼠T细胞。然而，c-Fos不是绝对需要外周T细胞的发育或功能，如使用小鼠所示，其中c-fos基因的两个拷贝都被靶向诱变破坏。c-Fos缺陷小鼠在胸腺细胞发育模式和外周T细胞增殖能力以及响应T细胞受体刺激产生几种细胞因子方面与野生型小鼠相当。我们的研究结果表明，其他Fos家族成员可能能够在功能上取代c-Fos在T细胞发育和细胞因子基因转录活化的T细胞。
The ubiquitous transcription factors Fos and Jun are rapidly induced in T cells stimulated through the T-cell antigen receptor and regulate transcription of cytokines, including interleukin 2, in activated T cells. Since positive and negative selection of thymocytes during T-cell development also depends on activation through the T-cell receptor, Fos and Jun may play a role in thymocyte development as well. Fos and Jun act at several regulatory elements in the interleukin 2 promoter, including the AP-1 and NFAT sites. Using antisera specific to individual Fos and Jun family members, we show that c-Fos as well as other Fos family members are present in the inducible AP-1 and NFAT complexes of activated murine T cells. Nevertheless, c-Fos is not absolutely required for the development or function of peripheral T cells, as shown by using mice in which both copies of the c-fos gene were disrupted by targeted mutagenesis. c-Fos-deficient mice were comparable to wild-type mice in their patterns of thymocyte development and in the ability of their peripheral T cells to proliferate and produce several cytokines in response to T-cell receptor stimulation. Our results suggest that other Fos family members may be capable of substituting functionally for c-Fos during T-cell development and cytokine gene transcription in activated T cells.