Department of Microbiology and Immunology, FOCIS Center of Excellence, McGill University and Research Institute of the McGill University Health Center, Montreal, Que., Canada H3G 1A4.
Autoimmunity. 2011 Dec;44(8):607-15. doi: 10.3109/08916934.2011.571730. Epub 2011 May 23.
A key component of the immune system is its ability to establish and maintain peripheral tolerance. Naturally occurring CD4+ CD25+ Foxp3+ regulatory T (nTreg) cells represent an important means by which this is accomplished, through their potent ability to suppress the actions of both CD4+ and CD8+ effector (Teff) cells in vitro and in vivo. We hypothesized that direct contact between nTreg and Teff cells is sufficient for nTreg cell-contact suppression. We first show that nTreg cell suppression is independent of APCs and their derived co-stimulatory signals. We then used a two-colour, lipid dye labelling and quantification approach to formally demonstrate that nTreg cells specifically form cell conjugates with responding T (Tresp) cells only under TCR activating conditions. Strikingly, activated CD4+ nTreg cells undergo progressive trogocytosis, a process by which membrane fragments are transferred from one cell subset to another, with Tresp cells more readily than Teff cells. These results are the first to show that nTreg cell cognate interactions with Tresp cells leads to trogocytosis between the cells, and the first to relate the degree of trogocytosis with the level of nTreg-mediated suppression.
免疫系统的一个关键组成部分是其建立和维持外周耐受的能力。天然存在的 CD4+CD25+Foxp3+调节性 T（nTreg）细胞代表了一种重要的手段，通过其在体外和体内抑制 CD4+和 CD8+效应（Teff）细胞的作用的强大能力来实现这一目标。我们假设 nTreg 与 Teff 细胞之间的直接接触足以实现 nTreg 细胞的接触抑制。我们首先表明，nTreg 细胞的抑制作用独立于 APCs 及其衍生的共刺激信号。然后，我们使用双色、脂质染料标记和定量方法来正式证明，只有在 TCR 激活条件下，nTreg 细胞才会特异性地与反应性 T（Tresp）细胞形成细胞共轭。引人注目的是，活化的 CD4+nTreg 细胞经历渐进性 trogocytosis，这是一个细胞亚群之间转移膜片段的过程，与 Teff 细胞相比，Tresp 细胞更容易发生 trogocytosis。这些结果首次表明，nTreg 细胞与 Tresp 细胞的同源相互作用导致细胞之间的 trogocytosis，并首次将 trogocytosis 的程度与 nTreg 介导的抑制水平相关联。
