Chen S, Liu D, Wu J, Xu B, Lu K, Zhu W, Chen M
Medical School of Southeast University, Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nan Jing, China.
Department of Urology, Affiliated Nanjing First Hospital, Nanjing Medical University, Nan Jing, China.
Transplant Proc. 2014 Jun;46(5):1642-8. doi: 10.1016/j.transproceed.2013.10.063.
Mammalian target of rapamycin (mTOR) signaling is crucial to the activation and proliferation of T cells. Memory T cells can significantly hinder the induction of transplant tolerance. Resent research demonstrates that mTOR signaling regulates the survival and function of memory T cells.
Naïve T cells were adoptively transferred to Rag(-/-) mice to generate similar memory T cells that undergo homeostatic proliferation. These memory T cells were then used to examine the effect of mTOR inhibition on the function of memory T cells. The effect of inhibiting mTOR signaling on the apoptosis of memory T cells was also examined.
Quantitative reverse-transcription polymerase chain reaction analysis showed that the expression of mTOR signaling was substantially lower in memory T cells. The levels of interferon-γ, interleukin (IL)-2, IL-4, and IL-10 decreased after mTOR inhibition; the expression of Bcl-2 increased in memory CD8(+) T cells and decreased in memory CD4(+) T cells; and Bax increased in memory CD4(+) T cells and decreased in memory CD8(+) T cells. Memory CD4(+) T cells were more sensitive to apoptotic cell death in this model after mTOR inhibition. Memory CD8(+) T cells were not affected by mTOR inhibition.
mTOR was crucial to homeostatic proliferation-induced memory T cells. The critical mechanisms of mTOR signaling inhibition are suppressed the functions of memory T cells and promoted the apoptosis of memory CD4(+) T cells.
雷帕霉素哺乳动物靶点（mTOR）信号传导对于T细胞的激活和增殖至关重要。记忆T细胞可显著阻碍移植耐受的诱导。近期研究表明，mTOR信号传导调节记忆T细胞的存活和功能。
将初始T细胞过继转移至Rag（-/-）小鼠，以产生经历稳态增殖的相似记忆T细胞。然后利用这些记忆T细胞检测mTOR抑制对记忆T细胞功能的影响。还检测了抑制mTOR信号传导对记忆T细胞凋亡的影响。
定量逆转录聚合酶链反应分析显示，记忆T细胞中mTOR信号传导的表达显著降低。mTOR抑制后，干扰素-γ、白细胞介素（IL）-2、IL-4和IL-10水平下降；记忆CD8（+）T细胞中Bcl-2表达增加，记忆CD4（+）T细胞中Bcl-2表达下降；记忆CD4（+）T细胞中Bax表达增加，记忆CD8（+）T细胞中Bax表达下降。在该模型中，mTOR抑制后记忆CD4（+）T细胞对凋亡性细胞死亡更敏感。记忆CD8（+）T细胞不受mTOR抑制的影响。
mTOR对于稳态增殖诱导的记忆T细胞至关重要。mTOR信号传导抑制的关键机制是抑制记忆T细胞的功能并促进记忆CD4（+）T细胞的凋亡。
