CD4+CD25+ Regulatory T Cells Attenuate the Phosphatidylinositol 3-Kinase/Akt Pathway in Antigen-Primed Immature CD8+ CTLs during Functional Maturation 1
CD4+CD25+ Regulatory T Cells Attenuate the Phosphatidylinositol 3-Kinase/Akt Pathway in Antigen-Primed Immature CD8+ CTLs during Functional Maturation 1
复制标题
DOI：
10.4049/jimmunol.174.10.5959
复制
发表时间：
2005-05
期刊：
影响因子：
--
通讯作者：
H. Kojima;Y. Kanno;H. Hase;T. Kobata
中科院分区：
文献类型：
--
作者：
H. Kojima;Y. Kanno;H. Hase;T. Kobata
本研究旨在确定CD 25 + CD 4+调节性T（Tr）细胞在CTL成熟和效应功能中的作用，使用小鼠CTL系和体外MLC。Tr细胞抑制CTL功能成熟，但对CTL效应子功能无影响。在补充有IL-2的CD 4+应答T细胞耗尽的MLC中，Tr细胞仅在培养的前2天内添加时抑制成熟CTL产生。Tr细胞下调活性Akt的水平，但在Ag引发的未成熟CTL中不下调STAT 5或ZAP 70。活性Akt的下调伴随着CTL细胞大小和IL-2 R α表达的减少。在Tr细胞耗尽的MLC中，产生的CTL表现出高水平的非特异性细胞毒性。我们的体外研究结果表明，Tr细胞调节功能性CTL成熟，通过控制PI 3 K/Akt途径产生最佳的Ag特异性免疫应答。
This study was designed to determine the role of CD25+CD4+ regulatory T (Tr) cells in CTL maturation and effector functions using a murine CTL line and in vitro MLC. Tr cells inhibited CTL functional maturation, but had no effect on CTL effector functions. In CD4+ responder T cell-depleted MLC supplemented with IL-2, Tr cells suppressed mature CTL generation only when added within the first 2 days of culture. Tr cells down-regulated levels of active Akt, but not STAT5 or ZAP70 in Ag-primed immature CTLs. Down-regulation of active Akt was accompanied by a reduction in CTL cell size and IL-2Rα expression. In Tr cell-depleted MLC, CTLs were generated that exhibited high levels of nonspecific cytotoxicity. Our in vitro findings suggest that Tr cells regulate functional CTL maturation to generate optimal Ag-specific immune responses through the control of the PI3K/Akt pathway.