Emory Transplant Center and Department of Surgery Emory Vaccine Center and Department of Microbiology and Immunology, Emory University, Atlanta, GA, USA.
Am J Transplant. 2011 Apr;11(4):654-9. doi: 10.1111/j.1600-6143.2011.03473.x.
Rapamycin has long been considered an immunosuppressive agent due to its antiproliferative effects on immune cells, and is currently used as a component of antirejection regimens in transplantation. Despite the large number of mechanistic and clinical studies investigating the impact of rapamycin on cell-mediated immunity, several paradoxes concerning rapamycin immunobiology remain. In particular, emerging evidence suggests that under certain circumstances rapamycin can exert immunostimulatory effects, boosting T cell responses in the face of pathogen infections and vaccines. Here, we review recent findings concerning the contradictory outcomes of rapamycin induced mTOR inhibition on CD4(+) and CD8(+) T cell responses in transplantation and protective immunity. These studies suggest that the conditions under which T cells are stimulated can profoundly modify the impact of rapamycin on antigen-specific T cell responses. Thus, further investigation into the cellular and molecular pathways underlying the dichotomous effects of rapamycin in transplantation is required to harness the full potential of this immunomodulatory agent to promote graft survival and maximize protective immunity.
雷帕霉素长期以来被认为是一种免疫抑制剂，因为它对免疫细胞具有抗增殖作用，目前被用作移植中抗排斥方案的一部分。尽管有大量的机制和临床研究调查了雷帕霉素对细胞介导免疫的影响，但雷帕霉素免疫生物学仍存在几个悖论。特别是，新出现的证据表明，在某些情况下，雷帕霉素可以发挥免疫刺激作用，在面对病原体感染和疫苗时增强 T 细胞反应。在这里，我们回顾了最近关于雷帕霉素诱导的 mTOR 抑制对移植和保护性免疫中 CD4(+)和 CD8(+)T 细胞反应的矛盾结果的发现。这些研究表明，刺激 T 细胞的条件可以极大地改变雷帕霉素对抗原特异性 T 细胞反应的影响。因此，需要进一步研究细胞和分子途径，以充分利用这种免疫调节剂来促进移植物存活并最大限度地提高保护性免疫。
