Institute of Hematology, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan 430022, China.
Autoimmunity. 2010 Jun;43(4):299-307. doi: 10.3109/08916930903405875.
CD4(+)CD25(+) regulatory T cells (Treg) are a unique population of T cells that maintain immune tolerance and are essential in host suppression of autoimmune diseases. Natural killer (NK) cells are an important component of the innate immune system and respond to insults. Recent studies demonstrate that NK cells may play a vital role during the onset and progression of certain autoimmune diseases. The decreased or abolished regulation by Treg cells on NK cells may lead to the abnormal autoimmune response. The purpose of this study was to investigate the suppressive effect of Foxp3-transduced CD4(+) T cells on NK cell functions, and thus to present a possible method for managing NK cell-related autoimmune abnormalities. This study showed that forced Foxp3 expression in polyclonal CD4(+) T cells could obtain Treg cells phenotype, including specifically expressing CD25, transforming growth factor (TGF-beta) and CTLA-4. Since NK cells have two major immunological properties--cytotoxicity and cytokine production, we observed that transduction-induced Treg cells decreased NK cell cytotoxicity obviously, and dramatically downregulated the interferon-gamma secretion of NK cell responding to IL-12 stimulation. Moreover, it was found that cell-cell interaction was essential for suppression of NK cell functions, and TGF-beta played a vital role in the inhibition process. These results indicate that the forced Foxp3 expression in polyclonal CD4(+) T cells could induce Treg cells and potentially inhibit NK cell functions.
CD4(+)CD25(+) 调节性 T 细胞（Treg）是一种独特的 T 细胞群体，可维持免疫耐受，在宿主抑制自身免疫性疾病中至关重要。自然杀伤（NK）细胞是先天免疫系统的重要组成部分，对刺激物作出反应。最近的研究表明，NK 细胞在某些自身免疫性疾病的发生和进展中可能发挥重要作用。Treg 细胞对 NK 细胞的调节作用降低或丧失可能导致异常的自身免疫反应。本研究旨在探讨 Foxp3 转导的 CD4(+)T 细胞对 NK 细胞功能的抑制作用，从而为管理 NK 细胞相关自身免疫异常提供一种可能的方法。本研究表明，在多克隆 CD4(+)T 细胞中强制表达 Foxp3 可获得 Treg 细胞表型，包括特异性表达 CD25、转化生长因子（TGF-β）和 CTLA-4。由于 NK 细胞具有两种主要的免疫学特性——细胞毒性和细胞因子产生，我们观察到诱导的 Treg 细胞明显降低了 NK 细胞的细胞毒性，并且显著下调了 NK 细胞对 IL-12 刺激的干扰素-γ分泌。此外，还发现细胞间相互作用对于抑制 NK 细胞功能至关重要，TGF-β在抑制过程中起着至关重要的作用。这些结果表明，在多克隆 CD4(+)T 细胞中强制表达 Foxp3 可诱导 Treg 细胞并可能抑制 NK 细胞功能。
