Siegmund Kerstin, Rückert Beate, Ouaked Nadia, Bürgler Simone, Speiser Andreas, Akdis Cezmi A, Schmidt-Weber Carsten B
Swiss Institute of Allergy and Asthma Research, University of Zurich, Davos, Switzerland.
J Immunol. 2009 Feb 15;182(4):2124-30. doi: 10.4049/jimmunol.0802271.
Forkhead box p3 (FOXP3) is known to program the acquisition of suppressive capacities in CD4(+) regulatory T cells (Treg), whereas its role in CD8(+) T cells is unknown. The current study investigates whether FOXP3 also acts as a Treg master switch in peripheral blood and tonsillar CD8(+) T cells. Single-cell analyses reveal the existence of a FOXP3(+)CD8(+) population in human tonsils, whereas FOXP3(+)CD8(+) T cells are rarely detected in peripheral blood. Tonsillar FOXP3(+)CD8(+) T cells exhibit a Treg phenotype with high CTLA-4 and CD45RO and low CD127 and CD69 expression. Interestingly, the tonsillar FOXP3(+)CD8(+) T cells are mostly CD25(negative) and some cells also express the proinflammatory cytokines TNF-alpha, IFN-gamma, or IL-17A. Particularly, IL-17A-expressing cells are present among FOXP3(+)CD8(+) T cells. Even though FOXP3 expression is at the detection limit in peripheral blood CD8(+) T cells ex vivo, it can be induced in vitro in naive CD8(+) T cells by polyclonal stimulation. The induced FOXP3(+)CD8(+) T cells are predominantly CD25(high) and CD28(high) and similar to tonsillar cells, they produce high levels of TNF-alpha, IFN-gamma, and granzyme B. However, IL-4 expression is mutually exclusive and IL-17A expression is not detectable. These FOXP3(+)CD8(+) T cells suppress the proliferation of CD4(+) T cells in cocultures, while showing no direct cytotoxic activity. In conclusion, the current study characterizes FOXP3-expressing CD8(+) T cells from human tonsils and shows that in vitro activation leads to FOXP3 expression in CD8(+) T cells and gain of suppressive activity.
已知叉头框蛋白P3（FOXP3）负责调控CD4(+)调节性T细胞（Treg）获得抑制能力，但其在CD8(+) T细胞中的作用尚不清楚。本研究旨在探究FOXP3在外周血和扁桃体CD8(+) T细胞中是否也作为Treg主开关发挥作用。单细胞分析显示人类扁桃体中存在FOXP3(+)CD8(+)细胞群，而在外周血中很少检测到FOXP3(+)CD8(+) T细胞。扁桃体FOXP3(+)CD8(+) T细胞表现出Treg表型，CTLA-4和CD45RO表达高，而CD127和CD69表达低。有趣的是，扁桃体FOXP3(+)CD8(+) T细胞大多为CD25阴性，一些细胞还表达促炎细胞因子TNF-α、IFN-γ或IL-17A。特别是，FOXP3(+)CD8(+) T细胞中存在表达IL-17A的细胞。尽管体外培养的外周血CD8(+) T细胞中FOXP3表达处于检测极限，但通过多克隆刺激可在体外将其诱导至初始CD8(+) T细胞中。诱导产生的FOXP3(+)CD8(+) T细胞主要为CD25高表达和CD28高表达，与扁桃体细胞相似，它们产生高水平的TNF-α、IFN-γ和颗粒酶B。然而，IL-4表达相互排斥且未检测到IL-17A表达。这些FOXP3(+)CD8(+) T细胞在共培养中抑制CD4(+) T细胞的增殖，但未表现出直接的细胞毒性活性。总之，本研究对人类扁桃体中表达FOXP3的CD8(+) T细胞进行了表征，并表明体外激活可导致CD8(+) T细胞中FOXP3表达及抑制活性的获得。
