PMID- 24935341 OWN - NLM STAT- MEDLINE DCOM- 20150226 LR - 20211203 IS - 1873-2623 (Electronic) IS - 0041-1345 (Linking) VI - 46 IP - 5 DP - 2014 Jun TI - Effect of inhibiting the signal of mammalian target of rapamycin on memory T cells. PG - 1642-8 LID - S0041-1345(14)00149-3 [pii] LID - 10.1016/j.transproceed.2013.10.063 [doi] AB - BACKGROUND: 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. MATERIALS AND METHODS: Naive 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. RESULTS: 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-gamma, 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. CONCLUSIONS: 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. CI - Copyright (c) 2014 Elsevier Inc. All rights reserved. FAU - Chen, S AU - Chen S AD - Medical School of Southeast University, Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nan Jing, China. FAU - Liu, D AU - Liu D AD - Medical School of Southeast University, Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nan Jing, China. FAU - Wu, J AU - Wu J AD - Department of Urology, Affiliated Nanjing First Hospital, Nanjing Medical University, Nan Jing, China. FAU - Xu, B AU - Xu B AD - Medical School of Southeast University, Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nan Jing, China. FAU - Lu, K AU - Lu K AD - Medical School of Southeast University, Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nan Jing, China. FAU - Zhu, W AU - Zhu W AD - Medical School of Southeast University, Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nan Jing, China. FAU - Chen, M AU - Chen M AD - Medical School of Southeast University, Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nan Jing, China. Electronic address: mingchen6308@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Transplant Proc JT - Transplantation proceedings JID - 0243532 RN - 0 (DNA Primers) RN - EC 2.7.1.1 (mTOR protein, mouse) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Animals MH - Base Sequence MH - DNA Primers MH - Flow Cytometry MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Reverse Transcriptase Polymerase Chain Reaction MH - Signal Transduction MH - TOR Serine-Threonine Kinases/*antagonists & inhibitors/metabolism EDAT- 2014/06/18 06:00 MHDA- 2015/02/27 06:00 CRDT- 2014/06/18 06:00 PHST- 2013/08/29 00:00 [received] PHST- 2013/10/28 00:00 [accepted] PHST- 2014/06/18 06:00 [entrez] PHST- 2014/06/18 06:00 [pubmed] PHST- 2015/02/27 06:00 [medline] AID - S0041-1345(14)00149-3 [pii] AID - 10.1016/j.transproceed.2013.10.063 [doi] PST - ppublish SO - Transplant Proc. 2014 Jun;46(5):1642-8. doi: 10.1016/j.transproceed.2013.10.063.