Bodor Josef, Fehervari Zoltan, Diamond Betty, Sakaguchi Shimon
Department of Medicine, Columbia University, College of Physicians and Surgeons, 1130 St. Nicholas Ave., New York, NY 10032, USA.
J Leukoc Biol. 2007 Jan;81(1):161-7. doi: 10.1189/jlb.0706474. Epub 2006 Oct 6.
How regulatory T (TR) cells dampen T cell responses remains unclear. Multiple modes of action have been proposed, including cell contact-dependent and/or cytokine-dependent mechanisms. Suppression may involve direct contact between TR cells and responder T cells. Alternatively, TR cells may act on dendritic cells to reduce their ability to prime T cells by modulating costimulation, inducing the secretion of suppressive cytokines or the increase of tryptophan metabolism. Here, we review emerging, novel mechanisms involved in contact-dependent, TR-mediated suppression of IL-2 production in responder CD25- T lymphocytes and the potential involvement of inducible cAMP early repressor (ICER) in this suppression. Finally, cytokines such as TGF-beta and IL-10, produced by TR cells or other cells, may exert local suppression, which can be conveyed by basic mechanism(s) acting in a similar manner as contact-dependent, TR-mediated suppression.
调节性T（TR）细胞如何抑制T细胞反应仍不清楚。人们提出了多种作用模式，包括细胞接触依赖性和/或细胞因子依赖性机制。抑制作用可能涉及TR细胞与反应性T细胞之间的直接接触。另外，TR细胞可能作用于树突状细胞，通过调节共刺激、诱导抑制性细胞因子的分泌或增加色氨酸代谢来降低其启动T细胞的能力。在这里，我们综述了参与接触依赖性、TR介导的反应性CD25-T淋巴细胞中IL-2产生抑制的新出现的机制，以及诱导型cAMP早期阻遏物（ICER）在这种抑制中的潜在作用。最后，TR细胞或其他细胞产生的细胞因子如TGF-β和IL-10可能发挥局部抑制作用，这可以通过与接触依赖性、TR介导的抑制作用类似的基本机制来实现。
