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Transplantation proceedings

Effect of inhibiting the signal of mammalian target of rapamycin on memory T cells.


PMID 24935341

Abstract

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.