Holderness Jeff, Hedges Jodi F, Daughenbaugh Katie, Kimmel Emily, Graff Jill, Freedman Brett, Jutila Mark A
Veterinary Molecular Biology, Montana State University, Bozeman, MT 59718, USA.
Crit Rev Immunol. 2008;28(5):377-402. doi: 10.1615/critrevimmunol.v28.i5.20.
Many pharmaceutical drugs arc isolated from plants used in traditional medicines, and new plant-derived pharmaceutical drugs continue to be identified. Relevant to this review, different plant-derived agonists for gammadelta T cells are described that impart effector functions upon distinct subsets of these cells. Recently, plant tannins have been defined as one class of gammadelta T cell agonist and appear to preferentially activate the mucosal population. Mucosal gammadelta T cells function to modulate tissue immune responses and induce epithelium repair. Select tannins, isolated from apple peel, rapidly induce immune gene transcription in gammadelta T cells, leading to cytokinc production and increased responsiveness to secondary signals. Activity of these tannin preparations tracks to the procyanidin fraction, with the procyanidin trimer (C1) having the most robust activity defined to date. The response to the procyanidins is evolutionarily conserved in that responses are seen with human, bovine, and murine gammadelta T cells, although human cells show less selectivity. Procyanidin-induced responses described in this review likely account for the expansion of mucosal gammadelta T cells seen in mice and rats fed soluble extracts of tannins. Use of procyanidins to activate gammadelta T cells may represent a novel approach for the treatment of tissue damage and autoimmune diseases.
许多药物是从传统医学中使用的植物中分离出来的,并且新的植物源药物也在不断被发现。与本综述相关的是,已描述了不同的植物源γδT细胞激动剂,它们能赋予这些细胞不同亚群效应功能。最近,植物单宁已被定义为一类γδT细胞激动剂,并且似乎优先激活黏膜群体。黏膜γδT细胞的功能是调节组织免疫反应并诱导上皮修复。从苹果皮中分离出的特定单宁能迅速诱导γδT细胞中的免疫基因转录,导致细胞因子产生并增强对二次信号的反应性。这些单宁制剂的活性追踪到原花青素部分,其中原花青素三聚体(C1)具有迄今为止所确定的最强活性。对原花青素的反应在进化上是保守的,因为人类、牛和小鼠的γδT细胞都有反应,尽管人类细胞的选择性较低。本综述中描述的原花青素诱导的反应可能解释了在喂食单宁可溶提取物的小鼠和大鼠中观察到的黏膜γδT细胞的扩增。使用原花青素激活γδT细胞可能代表一种治疗组织损伤和自身免疫性疾病的新方法。