Natural regulatory (CD4+CD25+FOXP+) T cells control the production of pro-inflammatory cytokines during Plasmodium chabaudi adami infection and do not contribute to immune evasion
Natural regulatory (CD4+CD25+FOXP+) T cells control the production of pro-inflammatory cytokines during Plasmodium chabaudi adami infection and do not contribute to immune evasion
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DOI：
10.1016/j.ijpara.2007.07.006
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发表时间：
2008-02-01
影响因子：
4
通讯作者：
Scorza, T.
中科院分区：
文献类型：
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作者：
Cambos, M.;Belanger, B.;Scorza, T.
在疟疾感染过程中，自然调节的CD4(+)CD25(+)FOXP(+)(Treg)细胞具有不同的功能。在这里，我们评估了Treg细胞在感染致死性(DS)和非致命性(DK)查鲍迪阿达米疟原虫过程中的作用，比较了寄生虫血症、炎症和贫血的水平。与寄生虫的毒力无关，在感染过程中，脾Treg细胞的数量增加，而激活的CD69(+)Treg细胞的绝对数在DS感染的小鼠中更高。体内清除CD25(+)T细胞，消除了80%的CD4(+)FOXP3(+)CD25(+)T细胞和60-70%的CD4(+)FOXP3(+)T细胞，显著减少了致死性疟疾小鼠的CD69(+)Treg细胞的数量。结果，后者的寄生虫负担和发病率较高，而感染非致命性寄生虫的动力学仍未受到影响。在没有Treg细胞的情况下，在致命性和非致命性感染的小鼠中，CD4(+)T细胞对寄生虫特异性的干扰素-伽马反应显著增加，而IL-2的产生只在非致命性疟疾的小鼠中被刺激。在CD25(+)T细胞耗尽后，感染小鼠CD90(-)细胞产生IL-10的能力也增强。有趣的是，在DS感染的小鼠中，检测到CD4(+)和CD90-淋巴细胞能够有效地诱导肿瘤坏死因子-α和干扰素-γ的产生，这些小鼠也比未耗尽的感染对照组更早出现严重的厌氧症。综上所述，我们的数据表明，自然Treg细胞的扩张和激活代表了对与致命性P.C.Adami相关的压倒性炎症的反调节反应。这种对感染的反应涉及TH1淋巴细胞以及来自先天免疫系统的细胞。(C)2007澳大利亚寄生虫学会有限公司出版。保留所有权利。
Different functions have been attributed to natural regulatory CD4(+)CD25(+)FOXP(+) (Treg) cells during malaria infection. Herein, we assessed the role for Treg cells during infections with lethal (DS) and non-lethal (DK) Plasmodium chabaudi adami parasites, comparing the levels of parasitemia, inflammation and anaemia. Independent of parasite virulence, the population of splenic Treg cells expanded during infection, and the absolute numbers of activated CD69(+) Treg cells were higher in DS-infected mice. In vivo depletion of CD25(+) T cells, which eliminated 80% of CD4(+)FOXP3(+)CD25(+) T cells and 60-70% of CD4(+)FOXP3(+) T cells, significantly decreased the number of CD69(+) Treg cells in mice with lethal malaria. As a result, higher parasite burden and morbidity were measured in the latter, whereas the kinetics of infection with non-lethal parasites remained unaffected. In the absence of Treg cells, parasite-specific IFN-gamma responses by CD4(+) T cells increased significantly, both in mice with lethal and non-lethal infections, whereas IL-2 production was only stimulated in mice with non-lethal malaria. Following the depletion of CD25(+) T cells, the production of IL-10 by CD90(-) cells was also enhanced in infected mice. Interestingly, a potent induction of TNF-alpha and IFN-gamma production by CD4(+) and CD90- lymphocytes was measured in DS-infected mice, which also suffered severe anaernia earlier than non-depleted infected controls. Taken together, our data suggest that the expansion and activation of natural Treg cells represent a counter-regulatory response to the overwhelming inflammation associated with lethal P. c. adami. This response to infection involves TH1 lymphocytes as well as cells from the innate immune system. (c) 2007 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.