Parasite-Antigen Driven Expansion of IL-5- and IL-5+ Th2 Human Subpopulations in Lymphatic Filariasis and Their Differential Dependence on IL-10 and TGFβ
Parasite-Antigen Driven Expansion of IL-5- and IL-5+ Th2 Human Subpopulations in Lymphatic Filariasis and Their Differential Dependence on IL-10 and TGFβ
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DOI：
10.1371/journal.pntd.0002658
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发表时间：
2014-01-01
影响因子：
3.8
通讯作者：
Babu, Subash
中科院分区：
文献类型：
--
作者：
Anuradha, Rajamanickam;George, Parakkal Jovvian;Babu, Subash
背景：最近在IL-5表达的基础上定义了两种不同的Th2亚群--IL-5(+)Th2亚群和IL-5(-)Th2亚群。方法：为了研究Th2亚群在慢性组织侵袭性寄生虫病(淋巴丝虫病)中的作用，我们检测了慢性组织侵袭性寄生虫病患者外周血中IL-5(+)、IL-4(+)、IL-13(+)、CD4(+)T细胞和IL-5(-)、IL-4、IL-13(+)、CD4(+)T细胞的频率。结果：丝虫感染者的Th2亚群自发表达的F-o和抗原诱导的F-o均显著高于非丝虫感染者和丝虫淋巴水肿者。有趣的是，IL-5(+)Th2细胞的F-o与嗜酸性粒细胞和中性粒细胞的绝对计数呈正相关，而在中性粒细胞亚群中，CD4(+)IL-5(-)Th2亚群的频率与寄生虫抗原特异性IgE和IgG4水平呈正相关。此外，阻断IL-10和/或转化生长因子β表明，这两种调节性细胞因子对不同的Th2亚群起相反的作用。结论：IL-5(+)和IL-5(-)Th2细胞在丝虫感染的免疫应答调节中起重要作用，这两种Th2亚群可能受不同的细胞因子受体介导的过程调节。
Background: Two different Th2 subsets have been defined recently on the basis of IL-5 expression - an IL-5(+)Th2 subset and an IL-5(-)Th2 subset in the setting of allergy. However, the role of these newly described CD4(+) T cells subpopulations has not been explored in other contexts.Methods: To study the role of the Th2 subpopulation in a chronic, tissue invasive parasitic infection (lymphatic filariasis), we examined the frequency of IL-5(+)IL-4(+)IL-13(+) CD4(+) T cells and IL-5(-)IL-4 IL-13(+) CD4(+) T cells in asymptomatic, infected individuals (INF) and compared them to frequencies (F-o) in filarial-uninfected (UN) individuals and to those with filarial lymphedema (CP).Results: INF individuals exhibited a significant increase in the spontaneously expressed and antigen-induced F-o of both Th2 subpopulations compared to the UN and CP. Interestingly, there was a positive correlation between the F-o of IL-5(+)Th2 cells and the absolute eosinophil and neutrophil counts; in addition there was a positive correlation between the frequency of the CD4(+)IL-5(-)Th2 subpopulation and the levels of parasite antigen - specific IgE and IgG4 in INF individuals. Moreover, blockade of IL-10 and/or TGF beta demonstrated that each of these 2 regulatory cytokines exert opposite effects on the different Th2 subsets. Finally, in those INF individuals cured of infection by anti-filarial therapy, there was a significantly decreased F-o of both Th2 subsets.Conclusions: Our findings suggest that both IL-5(+) and IL-5(-)Th2 cells play an important role in the regulation of immune responses in filarial infection and that these two Th2 subpopulations may be regulated by different cytokine-receptor mediated processes.