Pang W, Sun X, Feng H, Wang J, Cui L, Cao Y
Department of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, China.
Department of Microbiology and Parasitology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, China.
Parasite Immunol. 2016 Jul;38(7):439-50. doi: 10.1111/pim.12333.
An inappropriate immune response to parasite infection is one of the primary drivers of malaria pathogenesis. Regulatory T cells (Tregs), an important subset of CD4(+) T cells, can maintain self-tolerance and prevent autoimmune diseases. However, there is little consensus about their role in malaria pathogenesis. In this study, we transiently depleted Tregs (CD25(+) T cells) using an anti-CD25 mAb (7D4 clone) at different time points following Plasmodium chabaudi chabaudi AS infection in BALB/c mice and investigated the effect of depletion of Tregs in this model. In control mice, Tregs proliferated significantly and their suppressive function was enhanced after infection. IL-10 was increased drastically during infection. Depletion of Tregs at various time points can lead to divergent outcomes. When Tregs were depleted prior to or during the early phase of infection, most mice survived and had a robust Th1 immune response. In contrast, when Tregs were depleted close to peak parasitemia, all mice died as a result of inflammation. Taken together, these data suggest that in P. c. chabaudi AS-infected BALB/c mice, Tregs inhibit the Th1 response and macrophage activation, leading to increased parasite load; however, they also control inflammation-mediated pathology by secreting high levels of IL-10.
对寄生虫感染的不适当免疫反应是疟疾发病机制的主要驱动因素之一。调节性T细胞（Tregs）是CD4(+) T细胞的一个重要亚群，可维持自身耐受性并预防自身免疫性疾病。然而，关于它们在疟疾发病机制中的作用，目前尚无定论。在本研究中，我们在BALB/c小鼠感染恰氏疟原虫AS后不同时间点，使用抗CD25单克隆抗体（7D4克隆）短暂清除Tregs（CD25(+) T细胞），并研究了该模型中Tregs清除的影响。在对照小鼠中，感染后Tregs显著增殖，其抑制功能增强。感染期间IL-10急剧增加。在不同时间点清除Tregs可导致不同结果。当在感染前期或早期清除Tregs时，大多数小鼠存活并具有强烈的Th1免疫反应。相反，当在寄生虫血症接近峰值时清除Tregs，所有小鼠均因炎症死亡。综上所述，这些数据表明，在恰氏疟原虫AS感染的BALB/c小鼠中，Tregs抑制Th1反应和巨噬细胞活化，导致寄生虫负荷增加；然而，它们也通过分泌高水平的IL-10来控制炎症介导的病理过程。
