Pearce E J, Cheever A, Leonard S, Covalesky M, Fernandez-Botran R, Kohler G, Kopf M
Department of Microbiology and Immunology, NYSCVM, Cornell University, Ithaca 14853, USA.
Int Immunol. 1996 Apr;8(4):435-44. doi: 10.1093/intimm/8.4.435.
Immunopathology and immune responses to Schistosoma mansoni were examined in IL-4 -/- mice. IL-5 and IL-10 production by lymphoid cells stimulated with soluble egg antigen (SEA), peripheral eosinophilia and serum levels of soluble IL-4 receptor but not IgE were all significantly elevated over background normal levels in IL-4 -/- mice as a result of infection. Additionally, IL-10 and IL-5 in addition to IL-2 and IFN-gamma transcripts were equally evident in diseased liver tissue from infected IL-4 -/- and wild-type mice. Nevertheless, analysis of antigen-stimulated IL-2, IL-4, IL-5, IL-10 and IFN-gamma production by lymphoid organ cells from infected or egg-injected IL-4 -/- mice revealed a more Th1-like pattern of cytokine production (IFN-gamma > IL-5) than in (wild-type) mice in which a stronger type 2 response to SEA was detectable (IL-4, IL-5 > IFN-gamma). Despite this, at 8 and 16 weeks after infection, liver pathology, as indicated by the size, cellularity, cellular composition and collagen content of granulomas, was similar in IL-4 -/- and wild-type animals. As in wild-type animals, granuloma size at week 16 was smaller than at week 8, indicating that modulation had occurred in the absence of IL-4. Differences in pathology were seen only when eggs were experimentally embolized to the lungs, in which case IL-4 -/- mice made smaller granulomatous responses than did wild-type animals. These data clearly show that IL-4 is not necessary for the hepatic granuloma formation which occurs during experimental schistosomiasis.
在白细胞介素-4基因敲除（IL-4 -/-）小鼠中检测了曼氏血吸虫的免疫病理学和免疫反应。感染后，IL-4 -/-小鼠中，用可溶性虫卵抗原（SEA）刺激的淋巴细胞产生的白细胞介素-5（IL-5）和白细胞介素-10、外周血嗜酸性粒细胞增多以及可溶性白细胞介素-4受体的血清水平均显著高于背景正常水平，但免疫球蛋白E（IgE）水平未升高。此外，在感染的IL-4 -/-小鼠和野生型小鼠的患病肝组织中，白细胞介素-10、白细胞介素-5以及白细胞介素-2和干扰素-γ转录本同样明显。然而，对感染或注射虫卵的IL-4 -/-小鼠的淋巴器官细胞受抗原刺激后产生的白细胞介素-2、白细胞介素-4、白细胞介素-5、白细胞介素-10和干扰素-γ的分析显示，与可检测到对SEA有更强2型反应（白细胞介素-4、白细胞介素-5＞干扰素-γ）的（野生型）小鼠相比，其细胞因子产生呈现出更类似1型辅助性T细胞（Th1）的模式（干扰素-γ＞白细胞介素-5）。尽管如此，在感染后8周和16周，根据肉芽肿的大小、细胞数量、细胞组成和胶原含量所显示的肝病理学在IL-4 -/-小鼠和野生型动物中相似。与野生型动物一样，第16周时肉芽肿大小比第8周时小，表明在没有白细胞介素-4的情况下发生了调节。仅在实验性将虫卵栓塞到肺部时才观察到病理学差异，在这种情况下，IL-4 -/-小鼠产生的肉芽肿反应比野生型动物小。这些数据清楚地表明，白细胞介素-4对于实验性血吸虫病期间发生的肝脏肉芽肿形成并非必需。
