Interleukin 10 and dendritic cells are the main suppression mediators of regulatory T cells in human neurocysticercosis
Interleukin 10 and dendritic cells are the main suppression mediators of regulatory T cells in human neurocysticercosis
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DOI：
10.1111/cei.12709
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发表时间：
2016-02-01
影响因子：
4.6
通讯作者：
Adalid-Peralta, L.
中科院分区：
文献类型：
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作者：
Arce-Sillas, A.;Alvarez-Luquin, D. D.;Adalid-Peralta, L.
神经囊虫病是由猪带绦虫在中枢神经系统的建立引起的。据认为，在共同进化过程中，寄生虫发展出了调节宿主免疫反应的策略。本文对调节性T细胞在控制神经囊虫病免疫应答中的作用机制进行了研究。与对照组相比，神经囊虫病患者血液中CD4(+)CD45RO（+）叉头盒蛋白3(FoxP3)（高）和CD4(+)CD25（高）FoxP3(+)CD95（高）表型的调节性T细胞和非调节性CD4(+)CD45RO(+)FoxP3(med) T细胞水平较高。有趣的是，调节性T细胞表达更高水平的细胞毒性T淋巴细胞抗原4 （CTLA-4）、淋巴细胞活化基因3 （LAG-3）、程序性死亡1 （PD-1）和糖皮质激素诱导的肿瘤坏死因子受体（GITR），提示树突状细胞与细胞间的接触机制。此外，神经囊虫患者外周血中IL-10和调节性T细胞1 （Tr1）水平升高，提示调节性T细胞的作用机制涉及免疫调节细胞因子的释放。没有证据表明调节性T细胞在抑制增殖反应中的作用。神经囊虫病患者的抑制性调节性T细胞与晚期活化淋巴细胞(CD4（+)CD38(+)）呈负相关。我们的研究结果表明，在神经囊虫病期间，调节性T细胞可能通过与树突状细胞的细胞间接触和Tr1释放的白细胞介素(IL)-10来控制免疫反应，从而创造一个免疫调节环境，可能有利于猪囊虫的发育及其在中枢神经系统中的持久性。
Neurocysticercosis is caused by the establishment of Taenia solium cysticerci in the central nervous system. It is considered that, during co-evolution, the parasite developed strategies to modulate the host's immune response. The action mechanisms of regulatory T cells in controlling the immune response in neurocysticercosis are studied in this work. Higher blood levels of regulatory T cells with CD4(+)CD45RO(+)forkhead box protein 3 (FoxP3)(high) and CD4(+)CD25(high)FoxP3(+)CD95(high) phenotype and of non-regulatory CD4(+)CD45RO(+)FoxP3(med) T cells were found in neurocysticercosis patients with respect to controls. Interestingly, regulatory T cells express higher levels of cytotoxic T lymphocyte antigen 4 (CTLA-4), lymphocyte-activation gene 3 (LAG-3), programmed death 1 (PD-1) and glucocorticoid-induced tumour necrosis factor receptor (GITR), suggesting a cell-to-cell contact mechanism with dendritic cells. Furthermore, higher IL-10 and regulatory T cell type 1 (Tr1) levels were found in neurocysticercosis patients' peripheral blood, suggesting that the action mechanism of regulatory T cells involves the release of immunomodulatory cytokines. No evidence was found of the regulatory T cell role in inhibiting the proliferative response. Suppressive regulatory T cells from neurocysticercosis patients correlated negatively with late activated lymphocytes (CD4(+)CD38(+)). Our results suggest that, during neurocysticercosis, regulatory T cells could control the immune response, probably by a cell-to-cell contact with dendritic cells and interleukin (IL)-10 release by Tr1, to create an immunomodulatory environment that may favour the development of T. solium cysticerci and their permanence in the central nervous system.