Chen Guang, Liu Jun, Wang Qing-Hui, Wu Yi, Feng Hui, Zheng Wei, Guo Sheng-Yu, Li Dong-Mei, Wang Ji-Chun, Cao Ya-Ming
Department of Immunology, College of Basic Medical Sciences, China Medical University, Heping District, Shenyang, China.
Parasitology. 2009 Sep;136(10):1107-20. doi: 10.1017/S0031182009990370. Epub 2009 Jul 2.
The outcome of Plasmodium yoelii 17XL-infected BALB/c and DBA/2 mice, ranging from death to spontaneous cure, respectively, depends largely on the establishment of effective pro-inflammatory type 1 responses during the early stages of infection and associates with CD4(+)CD25(+)Foxp3(+)regulatory T cells (Tregs). Here, effects of Tregs were analysed on early P. yoelii 17XL infection in BALB/c and DBA/2 mice. In vivo depletion of Tregs significantly reversed the inhibited establishment of effective pro-inflammatory type 1 responses in BALB/c mice, indicating that this cell population contributed to the suppression of T-cell function in malaria. Moreover, the proportion and absolute numbers of IL-10-secreting Tregs in BALB/c mice were significantly higher than that found in DBA/2 mice by intracytoplasmic staining, and IL-10 production was correlated with the Tregs population. In addition, in vivo Tregs depletion decreased the production of IL-10 and the apoptosis of CD4+ T cells. Consistently, IL-10R blockade also had the same effect as that of Tregs depletion in P. yoelii 17XL-infected BALB/c mice. Our data demonstrate that Tregs perhaps have an important role in regulating pro-inflammatory type 1 responses in an IL-10-dependent manner and induce CD4+ T cell apoptosis during the early stage of P. yoelii 17XL infection.
约氏疟原虫17XL感染的BALB/c和DBA/2小鼠的结局分别为死亡和自发治愈,这在很大程度上取决于感染早期有效促炎1型反应的建立,并与CD4(+)CD25(+)Foxp3(+)调节性T细胞(Tregs)相关。在此,分析了Tregs对BALB/c和DBA/2小鼠早期约氏疟原虫17XL感染的影响。体内去除Tregs显著逆转了BALB/c小鼠中有效促炎1型反应建立的抑制,表明该细胞群体促成了疟疾中T细胞功能的抑制。此外,通过胞内染色发现,BALB/c小鼠中分泌IL-10的Tregs的比例和绝对数量显著高于DBA/2小鼠,且IL-10的产生与Tregs群体相关。另外,体内去除Tregs降低了IL-10的产生以及CD4+T细胞的凋亡。同样,在约氏疟原虫17XL感染的BALB/c小鼠中,阻断IL-10R也具有与去除Tregs相同的效果。我们的数据表明,Tregs可能在以IL-10依赖的方式调节促炎1型反应以及在约氏疟原虫17XL感染早期诱导CD4+T细胞凋亡方面发挥重要作用。