Use of rapamycin in the induction of tolerogenic dendritic cells.
Use of rapamycin in the induction of tolerogenic dendritic cells.
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DOI：
10.1007/978-3-540-71029-5_10
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发表时间：
2009-01-01
影响因子：
--
通讯作者：
Thomson, Angus W
中科院分区：
文献类型：
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作者：
Fischer, Ryan;Turnquist, Heth R;Thomson, Angus W
雷帕霉素（RAPA）是一种大环三烯抗生素前药，是一种临床使用的“耐受性保留”免疫抑制剂，可抑制T、B和NK细胞的活性。此外，树突状细胞（DC）的成熟抗性和耐受性可以通过RAPA调节得到支持和保存。小鼠骨髓（BM）来源的髓系DC （mDC）在临床相关浓度的RAPA （RAPA-DC）下繁殖，即使暴露于炎症刺激下，也会产生具有低水平MHC和显著减少共刺激分子（特别是CD86）的表型不成熟DC。RAPA-DC是T细胞的弱刺激物，可诱导同种异体反应性T细胞的低反应性和凋亡。一个有趣的观察结果是，RAPA-DC保留了刺激和丰富调节性T细胞（Treg）的能力。可能由于这些特性，同种异体抗原（alloAg）脉冲受体衍生的DC在啮齿动物移植模型中有效地破坏抗同种异体移植免疫反应，使其成为进一步研究其促进耐受性潜力的有吸引力的主题。
Rapamycin (RAPA), a macrocyclic triene antibiotic pro-drug, is a clinically-utilized 'tolerance-sparing' immunosuppressant that inhibits the activity of T, B, and NK cells. Furthermore, maturation-resistance and tolerogenic properties of dendritic cells (DC) can be supported and preserved by conditioning with RAPA. Propagation of murine bone marrow (BM)-derived myeloid DC (mDC) in clinically relevant concentrations of RAPA (RAPA-DC) generates phenotypically immature DC with low levels of MHC and significantly reduced co-stimulatory molecules (especially CD86), even when exposed to inflammatory stimuli. RAPA-DC are weak stimulators of T cells and induce hyporesponsiveness and apoptosis in allo-reactive T cells. An interesting observation has been that RAPA-DC retain the ability to stimulate and enrich the regulatory T cells (Treg). Presumably as a result of these properties, alloantigen (alloAg)-pulsed recipient-derived DC are effective in subverting anti-allograft immune responses in rodent transplant models, making them an attractive subject for further investigation of their tolerance-promoting potential.