Kang Shin Ae, Park Mi-Kyung, Cho Min Kyoung, Park Sang Kyun, Jang Min Seong, Yang Bo-Gie, Jang Myoung Ho, Kim Dong-Hee, Yu Hak Sun
Department of Parasitology, School of Medicine, Pusan National University, Yangsan, Republic of Korea; Immunoregulatory therapeutics group in Brain Busan 21 project, Yangsan, Republic of Korea.
Department of Parasitology, School of Medicine, Pusan National University, Yangsan, Republic of Korea.
PLoS Negl Trop Dis. 2014 Dec 18;8(12):e3410. doi: 10.1371/journal.pntd.0003410. eCollection 2014 Dec.
The recruitment of CD4+CD25+Foxp3+T (Treg) cells is one of the most important mechanisms by which parasites down-regulate the immune system.
METHODOLOGY/PRINCIPAL FINDINGS: We compared the effects of Treg cells from Trichinella spiralis-infected mice and uninfected mice on experimental allergic airway inflammation in order to understand the functions of parasite-induced Treg cells. After four weeks of T. spiralis infection, we isolated Foxp3-GFP-expressing cells from transgenic mice using a cell sorter. We injected CD4+Foxp3+ cells from T. spiralis-infected [Inf(+)Foxp3+] or uninfected [Inf(-)Foxp3+] mice into the tail veins of C57BL/6 mice before the induction of inflammation or during inflammation. Inflammation was induced by ovalbumin (OVA)-alum sensitization and OVA challenge. The concentrations of the Th2-related cytokines IL-4, IL-5, and IL-13 in the bronchial alveolar lavage fluid and the levels of OVA-specific IgE and IgG1 in the serum were lower in mice that received intravenous application of Inf(+)Foxp3+ cells [IV(inf):+(+) group] than in control mice. Some features of allergic airway inflammation were ameliorated by the intravenous application of Inf(-)Foxp3+ cells [IV(inf):+(-) group], but the effects were less distinct than those observed in the IV(inf):+(+) group. We found that Inf(+)Foxp3+ cells migrated to inflammation sites in the lung and expressed higher levels of Treg-cell homing receptors (CCR5 and CCR9) and activation markers (Klrg1, Capg, GARP, Gzmb, OX40) than did Inf(-)Foxp3+ cells.
CONCLUSION/SIGNIFICANCE: T. spiralis infection promotes the proliferation and functional activation of Treg cells. Parasite-induced Treg cells migrate to the inflammation site and suppress immune responses more effectively than non-parasite-induced Treg cells. The adoptive transfer of Inf(+)Foxp3+ cells is an effective method for the treatment and prevention of allergic airway diseases in mice and is a promising therapeutic approach for the treatment of allergic airway diseases.
募集CD4+CD25+Foxp3+T（调节性T）细胞是寄生虫下调免疫系统的最重要机制之一。
方法/主要发现：为了解寄生虫诱导的调节性T细胞的功能，我们比较了旋毛虫感染小鼠和未感染小鼠的调节性T细胞对实验性变应性气道炎症的影响。旋毛虫感染四周后，我们使用细胞分选仪从转基因小鼠中分离出表达Foxp3-GFP的细胞。在诱导炎症之前或炎症期间，我们将旋毛虫感染的[感染（+）Foxp3+]或未感染的[感染（-）Foxp3+]小鼠的CD4+Foxp3+细胞注入C57BL/6小鼠的尾静脉。通过卵清蛋白（OVA）-明矾致敏和OVA激发诱导炎症。接受静脉注射感染（+）Foxp3+细胞的小鼠[静脉注射（感染）：+（+）组]支气管肺泡灌洗液中Th2相关细胞因子IL-4、IL-5和IL-13的浓度以及血清中OVA特异性IgE和IgG1的水平低于对照小鼠。静脉注射感染（-）Foxp3+细胞[静脉注射（感染）：+（-）组]可改善变应性气道炎症的一些特征，但效果不如静脉注射（感染）：+（+）组明显。我们发现，与感染（-）Foxp3+细胞相比，感染（+）Foxp3+细胞迁移至肺部炎症部位，并表达更高水平的调节性T细胞归巢受体（CCR5和CCR9）和激活标志物（Klrg1、Capg、GARP、Gzmb、OX40）。
结论/意义：旋毛虫感染促进调节性T细胞的增殖和功能激活。寄生虫诱导的调节性T细胞迁移至炎症部位，比非寄生虫诱导的调节性T细胞更有效地抑制免疫反应。过继转移感染（+）Foxp3+细胞是治疗和预防小鼠变应性气道疾病的有效方法，也是治疗变应性气道疾病的一种有前景的治疗方法。
