Division of Neurology/Department of Medicine, University of Alberta, Edmonton, Alberta, T6G 2G3, Canada.
J Leukoc Biol. 2011 Jun;89(6):927-34. doi: 10.1189/jlb.1210654. Epub 2011 Mar 14.
MS lesions are characterized by destruction of myelin and significant neuronal and axonal loss. Preliminary studies with the use of T(regs) in the mouse model of MS have been extremely encouraging. However, recent studies with human cells have shown the presence of different subpopulations of T cells within the CD4(+)CD25(+)Foxp3(+) T cell phenotype, some of which do not have regulatory functions. These findings suggest a potential difference between mouse and human in the regulatory phenotype. Here, we show that human activated CD4(+)CD25(+)Foxp3(+) T cells are neurotoxic in vitro. These cells expressed high levels of the cytotoxic molecule GrB and had no suppressive effect. On the contrary, they produced IFN-γ and low IL-17, suggesting a shift toward a T(H)1 phenotype. Thus, our data confirm the presence of a nonregulatory cytotoxic subpopulation within the human CD4(+)CD25(+)Foxp3(+) T cells and suggest further studies on the human regulatory phenotype prior to any potential therapeutic application.
多发性硬化症（MS）病变的特征是髓鞘破坏以及显著的神经元和轴突丢失。在 MS 的小鼠模型中使用 T（regs）进行的初步研究非常令人鼓舞。然而，最近对人类细胞的研究表明，在 CD4(+)CD25(+)Foxp3(+)T 细胞表型中存在不同的 T 细胞亚群，其中一些不具有调节功能。这些发现表明，在调节表型方面，小鼠和人类之间可能存在差异。在这里，我们表明人类激活的 CD4(+)CD25(+)Foxp3(+)T 细胞在体外具有神经毒性。这些细胞表达高水平的细胞毒性分子 GrB，并且没有抑制作用。相反，它们产生 IFN-γ和低水平的 IL-17，表明向 T(H)1 表型转变。因此，我们的数据证实了人类 CD4(+)CD25(+)Foxp3(+)T 细胞中存在非调节性细胞毒性亚群，并建议在任何潜在的治疗应用之前对人类调节表型进行进一步研究。
