Schistosome-infected IL-4 receptor knockout (KO) mice, in contrast to IL-4 KO mice, fail to develop granulomatous pathology while maintaining the same lymphokine expression profile.
Schistosome-infected IL-4 receptor knockout (KO) mice, in contrast to IL-4 KO mice, fail to develop granulomatous pathology while maintaining the same lymphokine expression profile.
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DOI：
10.4049/jimmunol.163.1.337
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发表时间：
1999-07
影响因子：
4.4
通讯作者：
Dragana Jankovic;M. Kullberg;N. Noben-Trauth;P. Caspar;J. Ward;A. Cheever;W. Paul;A. Sher
中科院分区：
文献类型：
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作者：
Dragana Jankovic;M. Kullberg;N. Noben-Trauth;P. Caspar;J. Ward;A. Cheever;W. Paul;A. Sher
Th2 淋巴细胞被认为在曼氏血吸虫感染诱导的免疫病理学中起主要作用。然而，受感染的 IL-4 敲除 (KO) 小鼠和野生型 (wt) 小鼠会出现大小相当的卵肉芽肿。为了进一步研究 Th2 反应在卵子病理学中的功能，我们研究了 IL-4Rα 缺陷小鼠，这些小鼠对 IL-4 和 IL-13 均无反应。与IL-4 KO动物形成鲜明对比的是，尽管残留卵病灶中存在CD3+ T细胞，但受感染的IL-4Rα KO小鼠仅出现极少量的肝肉芽肿和纤维化。此外，这些动物和 IL-4 KO 小鼠的肝脏淋巴因子 mRNA 水平相当。此外，受感染的IL-4Rα缺陷型、IL-4缺陷型和野生型动物产生了相似的卵Ag特异性IgG抗体滴度，这表明CD4依赖性Th活性在KO小鼠中是完整的。正如预期的那样，两组缺陷动物的肠系膜淋巴结培养物中 IFN-γ 分泌均强烈上调，这一变化反映在血清 IgG2a 和 IgG2b Ab 水平的增加。令人惊讶的是，受感染的IL-4Rα KO小鼠中Th2细胞因子的产生并没有被消除，而只是减少，并且与之前在IL-4 KO动物中记录的相似。这种残留的 Th2 反应可能解释了 IL-4 KO 小鼠产生卵肉芽肿的能力，而 IL-4Rα 缺陷的动物不能形成卵肉芽肿，因为它们缺乏对相同细胞因子配体的反应。总而言之，这些发现表明，血吸虫病的组织病理学除了卵特异性 CD4+ 淋巴细胞外，还需要以前未被识别的 IL-4Rα+ 非 T 细胞效应细胞群。
Th2 lymphocytes have been postulated to play a major role in the immunopathology induced by Schistosoma mansoni infection. Nevertheless, infected IL-4 knockout (KO) and wild-type (wt) mice develop egg granulomas comparable in size. To further investigate the function of the Th2 response in egg pathology we studied IL-4Ralpha-deficient mice, which are nonresponsive to both IL-4 and IL-13. In striking contrast to IL-4 KO animals, infected IL-4Ralpha KO mice developed only minimal hepatic granulomas and fibrosis despite the presence of CD3+ T cells in the residual egg lesions. Moreover, liver lymphokine mRNA levels in these animals and IL-4 KO mice were equivalent. In addition, infected IL-4Ralpha-deficient, IL-4-deficient, and wt animals developed similar egg Ag-specific IgG Ab titers, arguing that CD4-dependent Th activity is intact in KO mice. As expected, IFN-gamma secretion was strongly up-regulated in mesenteric lymph node cultures from both groups of deficient animals, a change reflected in increased serum IgG2a and IgG2b Ab levels. Surprisingly, Th2 cytokine production in infected IL-4Ralpha KO mice was not abolished but was only reduced and resembled that previously documented in IL-4 KO animals. This residual Th2 response is likely to explain the ability of IL-4 KO mice to generate egg granulomas, which cannot be formed in IL-4Ralpha-deficient animals because of their lack of responsiveness to the same cytokine ligands. Taken together, these findings argue that tissue pathology in schistosomiasis requires, in addition to egg-specific CD4+ lymphocytes, a previously unrecognized IL-4Ralpha+ non-T cell effector population.