Enforced expression of Bcl-2 partially restores cell numbers but not functions of TCRgammadelta intestinal intraepithelial T lymphocytes in IL-15-deficient mice.
Enforced expression of Bcl-2 partially restores cell numbers but not functions of TCRgammadelta intestinal intraepithelial T lymphocytes in IL-15-deficient mice.
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DOI：
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发表时间：
2007
影响因子：
4.4
通讯作者：
K. Nakazato;H. Yamada;T. Yajima;Yoshiko Kagimoto;H. Kuwano;Y. Yoshikai
中科院分区：
文献类型：
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作者：
K. Nakazato;H. Yamada;T. Yajima;Yoshiko Kagimoto;H. Kuwano;Y. Yoshikai
IL-15敲除（KO）小鼠的TCRgammadelta肠上皮内T淋巴细胞（i-IEL）数量严重减少，提示IL-15信号在i-IEL的发展或维持中是必需的。为了确定生存信号通过Bcl-2参与IL-15介导的TCRgammadelta i-IEL的稳态，我们将Bcl-2转基因引入IL-15 KO小鼠。与IL-15 KO小鼠相比，Bcl-2转基因（Tg） x IL-15 KO小鼠TCRgammadelta i-IEL的原位凋亡减少。强制表达Bcl-2可部分恢复il - 15ko小鼠中TCRgammadelta i-IEL的数量。然而，TCRgammadelta i-IEL的效应功能，包括细胞因子的产生和细胞毒活性，在Bcl-2 Tg x IL-15 KO小鼠中没有恢复。重要的是，Bcl-2 Tg x IL-15 KO小鼠中的TCRgammadelta i-IEL表达的eomesodermin水平降低，eomesodermin是NK细胞和CD8(+) T细胞效应功能的关键转录因子。与TCRgammadelta i-IEL类似，强行表达Bcl-2可以恢复IL-15 KO小鼠中NK细胞的数量，但不能恢复NK细胞的功能。这些结果表明，bcl -2介导的生存信号参与了IL-15介导的tcrgammadta i-IEL和NK细胞的稳态，但IL-15的其他信号对于诱导转录因子（如eomesodermin）发挥其效应功能至关重要。
IL-15 knockout (KO) mice have severely reduced numbers of TCRgammadelta intestinal intraepithelial T lymphocytes (i-IEL), suggesting requirements of IL-15 signaling in the development or maintenance of i-IEL. To determine an involvement of survival signals via Bcl-2 in IL-15-mediated homeostasis of TCRgammadelta i-IEL, we introduced a bcl-2 transgene into IL-15 KO mice. In situ apoptosis of TCRgammadelta i-IEL was decreased in Bcl-2 transgenic (Tg) x IL-15 KO mice compared with IL-15 KO mice. The enforced expression of Bcl-2 partially restored the numbers of TCRgammadelta i-IEL in IL-15 KO mice. However, effector functions of TCRgammadelta i-IEL, including cytokine production and cytotoxic activity, were not recovered in Bcl-2 Tg x IL-15 KO mice. Importantly, TCRgammadelta i-IEL in Bcl-2 Tg x IL-15 KO mice expressed a reduced level of eomesodermin, a transcription factor critical for effector functions of NK cells and CD8(+) T cells. Similar to the case of TCRgammadelta i-IEL, enforced expression of Bcl-2 restored the numbers but not the functions of NK cells in IL-15 KO mice. These results suggest that Bcl-2-mediated survival signal is involved in the IL-15-mediated homeostasis of TCRgammadelta i-IEL and NK cells, but other signals from IL-15 are critical for inducing transcription factors, such as eomesodermin for their effector functions.