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原发性肺泡型棘球蚴病中B细胞和T细胞免疫反应的实验研究

Experimental investigations on the B and T cell immune response in primary alveolar echinococcosis.

作者信息

Bauder B, Auer H, Schilcher F, Gabler C, Romig T, Bilger B, Aspöck H

机构信息

Department of Medical Parasitology, Clinical Institute of Hygiene, University of Vienna, Vienna, Austria.

出版信息

Parasite Immunol. 1999 Aug;21(8):409-21. doi: 10.1046/j.1365-3024.1999.00241.x.

DOI:10.1046/j.1365-3024.1999.00241.x
PMID:10417675
Abstract

Susceptibility/resistance of the intermediate host to alveolar echinococcosis (AE) seems to be based on hitherto unknown immunological mechanisms, possibly involving the activation of different CD4+ T cell immune responses (Th1/Th2). Mice of two strains previously characterized as 'susceptible' (C57BL/6 J) and 'resistant' (C57BL/10 J) to secondary AE were orally infected with eggs of Echinococcus multilocularis and the course of infection was analysed by macroscopical, pathohistological and immunohistochemical examinations of the lymphocytes and cytokines participating in the periparasitic granulomas and by serological examinations of cytokines and E. multilocularis-specific antibodies. Although differences in the extent of parasitic growth were seen between the two groups, the composition of the granulomas was quite similar with CD4+ cells being the dominant lymphocyte subpopulation, succeeded by B cells and CD8+ cells. Interferon (IFN)-gamma-, interleukin (IL)-2- and IL-4-expressing cells could not be detected in the lesions of the early phase of the infection, possibly indicating the host's immunosuppression, but were present at the end. IL-10 was the most prominent cytokine throughout the course of the disease. Serological analyses of the cytokine concentrations revealed small amounts at the beginning and high levels at the end of the infection. The pattern of cytokine response was similar for IL-4 in both strains, but different for IL-2 and IL-10 in the late phase, when the C57BL/10 J strain developed higher levels than the C57BL/6 J strain. Correspondingly only small amounts of immunoglobulin (Ig)M, IgG1, IgG2a and IgG3 could be detected at the beginning of disease, followed by higher levels at the end. The courses of antibody titres were similar in both groups except IgG3, which was more pronounced in the C57BL/10 J strain. Parasite-specific IgG2b could neither be detected in the C57BL/6 J nor in the C57BL/10 J strain by the test system used. The results of the study suggest both subsets of CD4+ T cells (Th1 and Th2) being involved in murine primary alveolar echinococcosis. A strict differentiation of mice in susceptible and resistant animals based on the activation of different CD4+ T cell immune responses (Th1 'resistant' and Th2 'susceptible') should be avoided.

摘要

中间宿主对泡型包虫病(AE)的易感性/抗性似乎基于迄今未知的免疫机制,可能涉及不同CD4 + T细胞免疫反应(Th1/Th2)的激活。将先前被鉴定为对继发性AE“易感”(C57BL/6 J)和“抗性”(C57BL/10 J)的两个品系的小鼠经口感染多房棘球绦虫虫卵,并通过对参与寄生虫周围肉芽肿的淋巴细胞和细胞因子进行宏观、病理组织学和免疫组织化学检查,以及对细胞因子和多房棘球绦虫特异性抗体进行血清学检查来分析感染过程。尽管两组之间在寄生虫生长程度上存在差异,但肉芽肿的组成非常相似,CD4 +细胞是主要的淋巴细胞亚群,其次是B细胞和CD8 +细胞。在感染早期的病变中未检测到表达干扰素(IFN)-γ、白细胞介素(IL)-2和IL-4的细胞,这可能表明宿主处于免疫抑制状态,但在后期存在。IL-10是疾病全过程中最突出的细胞因子。细胞因子浓度的血清学分析显示,感染开始时含量低,结束时含量高。两种品系中IL-4的细胞因子反应模式相似,但在后期IL-2和IL-10的反应模式不同,此时C57BL/10 J品系的水平高于C57BL/6 J品系。相应地,在疾病开始时仅检测到少量免疫球蛋白(Ig)M、IgG1、IgG2a和IgG3,随后在结束时水平升高。除IgG3外,两组抗体滴度的变化过程相似,IgG3在C57BL/10 J品系中更为明显。在所使用的检测系统中,在C57BL/6 J品系和C57BL/10 J品系中均未检测到寄生虫特异性IgG2b。研究结果表明,CD4 + T细胞的两个亚群(Th1和Th2)均参与小鼠原发性泡型包虫病。应避免基于不同CD4 + T细胞免疫反应(Th1“抗性”和Th2“易感”)的激活对小鼠进行易感性和抗性动物的严格区分。

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