Institute of Immunology, Tsinghua University School of Medicine, Beijing 100084, China.
J Immunol. 2013 Jun 15;190(12):6145-54. doi: 10.4049/jimmunol.1300060. Epub 2013 May 15.
Regulatory T cells can restrict the uncontrolled immune response and inflammation, avoiding pathologic immune injury to the host and thus playing important roles in the maintenance of immune homeostasis. Until recently, many subsets of CD4 and CD8 regulatory T cells have been reported. In this study, we identified CD11c(high)CD8(+) T cells as a new subset of CD8(+) regulatory T cells. During Listeria monocytogenes and Staphylococcus aureus infection, two subsets of CD8 T cells were classified according to the expression level of CD11c, including CD11c(low)CD8(+) and CD11c(high)CD8(+) T cells. CD11c(low)CD8(+) T cells, existing during the whole period of infection, act as conventional activated T cells to kill target cells in a perforin-dependent manner. Interestingly, CD11c(high)CD8(+) T cells appeared only at a late stage of infection, expressed relatively high CD122 and low CD69, did not secrete IFN-γ, IL-10, TGF-β, and exhibited much more potent cytotoxicity against target cells via Fas ligand-Fas pathway in an Ag-independent manner. Ligation of CD11c was important in the cytotoxicity of CD11c(high)CD8(+) T cells. Furthermore, CD11c(high)CD8(+) T cells could directly kill the activated CD4 T cells both in vitro and in vivo, whereas CD11c(low)CD8(+) T cells could not. Thus, we identified an infection-induced new subset of CD11c(high)CD8(+) regulatory T cells, which might contribute to protect host from pathological immune injure. Our results indicate that CD11c(+)CD8(+) T cells are constitute a heterogeneous population that can be divided further into regulatory CD11c(high)CD8(+) T cell subset and effector CD11c(low)CD8(+) T cell subset, thus adding insight to the role of CD8 T cells in immune response and regulation.
调节性 T 细胞可以限制不受控制的免疫反应和炎症，避免宿主发生病理性免疫损伤，从而在维持免疫稳态方面发挥重要作用。直到最近，人们已经报道了许多 CD4 和 CD8 调节性 T 细胞亚群。在这项研究中，我们鉴定出 CD11c(high)CD8(+)T 细胞是 CD8(+)调节性 T 细胞的一个新亚群。在李斯特菌和金黄色葡萄球菌感染期间，根据 CD11c 的表达水平，将两种 CD8 T 细胞分为两个亚群，包括 CD11c(low)CD8(+)和 CD11c(high)CD8(+)T 细胞。CD11c(low)CD8(+)T 细胞在整个感染期间存在，作为常规激活的 T 细胞以依赖穿孔素的方式杀死靶细胞。有趣的是，CD11c(high)CD8(+)T 细胞仅在感染后期出现，表达相对较高的 CD122 和较低的 CD69，不分泌 IFN-γ、IL-10 和 TGF-β，并通过 Fas 配体-Fas 途径以非抗原依赖的方式对靶细胞表现出更强的细胞毒性。CD11c 的结合对 CD11c(high)CD8(+)T 细胞的细胞毒性很重要。此外，CD11c(high)CD8(+)T 细胞可以在体外和体内直接杀死激活的 CD4 T 细胞，而 CD11c(low)CD8(+)T 细胞则不能。因此，我们鉴定出一种感染诱导的新型 CD11c(high)CD8(+)调节性 T 细胞亚群，它可能有助于保护宿主免受病理性免疫损伤。我们的研究结果表明，CD11c(+)CD8(+)T 细胞是一个异质性群体，可进一步分为调节性 CD11c(high)CD8(+)T 细胞亚群和效应性 CD11c(low)CD8(+)T 细胞亚群，从而为 CD8 T 细胞在免疫反应和调节中的作用提供了新的认识。
