Generation of highly suppressive adaptive CD8+CD25+FOXP3+ regulatory T cells by continuous antigen stimulation
Generation of highly suppressive adaptive CD8+CD25+FOXP3+ regulatory T cells by continuous antigen stimulation
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DOI：
10.1002/eji.200737529
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发表时间：
2008-03-01
影响因子：
5.4
通讯作者：
Aandahl, Einar Martin
中科院分区：
文献类型：
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作者：
Mahic, Milada;Henjum, Karen;Aandahl, Einar Martin
CD4(+)CD25(-) T细胞的连续抗原刺激导致适应性CD4(+)CD25(+)FOXP3(+)调节性T(TR)细胞的产生。在这里，我们发现，在CD14(+)单核细胞存在的情况下，通过连续抗原刺激，可以以相同的方式产生高度抑制的适应性CD8(+)CD25(+)FOXP3(+) T细胞。在刺激过程中，免疫抑制特性的获得与细胞毒性分子的上调和表达同时发生。 CD8(+)TR细胞抑制CD4(+)和CD8(+)T细胞增殖和细胞因子产生，但不改变CD8(+)效应T细胞中颗粒酶A和颗粒酶B或穿孔素的表达。尽管CD8(+)TR细胞表达前列腺素E-2、IL-10和TGF-β，但其抑制机制与这些可溶性因子无关。与适应性 CD4(+) T-R 细胞相比，CD8(+) TR 细胞主要通过接触依赖性机制进行抑制，这一点从 Transwell 实验中可以明显看出。然而，CTLA-4、CD80 和 CD86 的阻断抗体都不能逆转 CD8(+) T-R 介导的抑制，表明这些细胞必须采用其他机制。
Continuous antigen stimulation of CD4(+)CD25(-) T cells leads to generation of adaptive CD4(+)CD25(+)FOXP3(+) regulatory T (TR) cells. Here, we show that highly suppressive adaptive CD8(+)CD25(+)FOXP3(+) T cells can be generated in the same manner by continuous antigen stimulation in the presence of CD14(+) monocytes. During the course of stimulation, acquisition of immunosuppressive properties develops in parallel with up-regulation and expression of cytotoxic molecules. The CD8(+) TR cells inhibit CD4(+) and CD8(+) T cell proliferation and cytokine production, but do not alter the expression of granzyme A and granzyme B or perforin in CD8(+) effector T cells. Although, the CD8(+) TR cells express prostaglandin E-2, IL-10 and TGF-beta, the mechanism of suppression was independent of these soluble factors. In contrast to adaptive CD4(+) T-R cells, the CD8(+) TR cells suppress mainly by a contact-dependent mechanism as evident from transwell experiments. However, neither blocking antibodies to CTLA-4, CD80 nor CD86 could reverse CD8(+) T-R-mediated suppression, indicating that other mechanism(s) must be employed by these cells.