Enforced expression of Bcl-2 partially restores cell numbers but not functions of TCRγδ intestinal intraepithelial T lymphocytes in IL-15-deficient mice
Enforced expression of Bcl-2 partially restores cell numbers but not functions of TCRγδ intestinal intraepithelial T lymphocytes in IL-15-deficient mice
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DOI：
10.4049/jimmunol.178.2.757
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发表时间：
2007-01-15
影响因子：
4.4
通讯作者：
Yoshikai, Yasunobu
中科院分区：
文献类型：
--
作者：
Nakazato, Kenji;Yamada, Hisakata;Yoshikai, Yasunobu
IL-15 敲除 (KO) 小鼠的 TCR γ δ 肠上皮内 T 淋巴细胞 (i-IEL) 数量严重减少，表明 i-IEL 的发育或维持需要 IL-15 信号传导。为了确定通过 Bcl-2 的生存信号参与 IL-15 介导的 TCR-gamma delta i-IEL 稳态，我们将 bcl-2 转基因引入 IL-15 KO 小鼠中。与 IL-15 KO 小鼠相比，Bcl-2 转基因 (Tg) x IL-15 KO 小鼠中 TCR gamma delta i-IEL 的原位凋亡减少。 Bcl-2 的强制表达部分恢复了 11-15 KO 小鼠中 TCR gamma delta i-IEL 的数量。然而，在 Bcl-2 Tg x IL-15 KO 小鼠中，TCR gamma delta i-IEL 的效应功能（包括细胞因子产生和细胞毒活性）并未恢复。重要的是，Bcl-2 Tg x IL-15 KO 小鼠中的 TCR gamma delta i-IEL 表达的脱中胚蛋白水平降低，而脱中胚蛋白是对 NK 细胞和 CD8(+) T 细胞的效应功能至关重要的转录因子。与 TCR gamma delta i-IEL 的情况类似，Bcl-2 的强制表达恢复了 IL-15 KO 小鼠中 NK 细胞的数量，但没有恢复其功能。这些结果表明，Bcl-2 介导的生存信号参与了 TCR gamma delta i-IEL 和 NK 细胞的 IL-15 介导的稳态，但来自 11-15 的其他信号对于诱导转录因子（例如脱中胚层蛋白的效应功能）至关重要。
IL-15 knockout (KO) mice have severely reduced numbers of TCR gamma delta 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 TCR-gamma delta i-IEL, we introduced a bcl-2 transgene into IL-15 KO mice. In situ apoptosis of TCR gamma delta 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 TCR gamma delta i-IEL in 11-15 KO mice. However, effector functions of TCR gamma delta i-IEL., including cytokine production and cytotoxic activity, were not recovered in Bcl-2 Tg x IL-15 KO mice. Importantly, TCR gamma delta 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 TCR gamma delta 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 TCR gamma delta i-IEL and NK cells, but other signals from 11-15 are critical for inducing transcription factors, such as eomesodermin for their effector functions.