Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico.
Eur J Immunol. 2011 Dec;41(12):3529-41. doi: 10.1002/eji.201141507. Epub 2011 Oct 20.
Acute Toxoplasma gondii infection comprises an immunosuppression stage, characterized by a reduction in T-cell proliferation in vitro. Treg cells maintain the homeostasis of the immune system, but their role in T. gondii-induced suppression has not been addressed. We show herein that immunosuppression, affecting both CD4(+) and CD8(+) T-cell proliferation, concurs with a reduction in Treg-cell number. The residual Treg cells, however, are activated and display an increased suppressive capacity. We show that selective elimination of Treg cells using Foxp3(EGFP) mice leads to a full recovery of CD4(+) and CD8(+) T-cell proliferation. After Treg-cell removal, a reduced production of IL-10 was observed, but IL-2 levels were unchanged. The numbers of IL-10-producing Treg cells also increased during infection, although the in vitro neutralization of this cytokine did not modify T-cell proliferation, suggesting that IL-10 does not mediate the Treg-mediated suppression. However, addition of rIL-2 in vitro fully restored T-cell proliferation from infected animals. Thus, we show that Treg cells mediate the T-cell suppression observed during acute T. gondii infection through an IL-2-dependent mechanism. Our results provide novel insights into the regulation of the immune response against T. gondii.
急性弓形体感染包括一个免疫抑制阶段，其特征是体外 T 细胞增殖减少。调节性 T 细胞（Treg 细胞）维持着免疫系统的稳态，但它们在弓形虫诱导的抑制中的作用尚未得到解决。我们在此表明，免疫抑制影响 CD4(+)和 CD8(+)T 细胞的增殖，同时 Treg 细胞数量减少。然而，残留的 Treg 细胞被激活并表现出增强的抑制能力。我们表明，使用 Foxp3(EGFP)小鼠选择性消除 Treg 细胞可导致 CD4(+)和 CD8(+)T 细胞增殖完全恢复。在 Treg 细胞去除后，观察到 IL-10 的产生减少，但 IL-2 水平不变。在感染期间，IL-10 产生的 Treg 细胞数量也增加，尽管体外中和这种细胞因子不会改变 T 细胞增殖，表明 IL-10 不介导 Treg 介导的抑制。然而，体外添加 rIL-2 可完全恢复来自感染动物的 T 细胞增殖。因此，我们表明 Treg 细胞通过依赖 IL-2 的机制介导急性弓形体感染期间观察到的 T 细胞抑制。我们的结果为调节针对弓形虫的免疫反应提供了新的见解。
