Expression of class II, but not class I, major histocompatibility complex molecules is required for granuloma formation in infection with Schistosoma mansoni
Expression of class II, but not class I, major histocompatibility complex molecules is required for granuloma formation in infection with Schistosoma mansoni
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DOI：
10.1002/eji.1830270518
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发表时间：
1997-03-01
影响因子：
5.4
通讯作者：
Stadecker, MJ
中科院分区：
文献类型：
--
作者：
Hernandez, HJ;Wang, Y;Stadecker, MJ
先前的研究表明血吸虫病的肉芽肿性炎症是由对寄生虫卵抗原致敏的CD 4（+）T辅助淋巴细胞介导的。然而，CD 8（+）T细胞也经常与对虫卵的免疫反应有关。为了更精确地检测CD 4（+）和CD 8（+）T细胞在溶酶体感染病理学中的作用，我们使用了在主要组织相容性复合体（MHC）II类或I类分子中具有靶向突变的小鼠。这些突变分别导致CD 4（+）和CD 8（+）T细胞的实际缺失。结果清楚地表明，寄生虫体感染的MHC II类突变小鼠未能在寄生虫卵周围形成肉芽肿。相比之下，感染的MHC I类突变小鼠表现出特征性肉芽肿病变，与野生型对照小鼠相当。此外，来自MHC类IT突变小鼠的淋巴细胞不能以增殖或细胞因子[干扰素-γ，白细胞介素（IL）-4，IL-10]应答与卵抗原反应;它们也不能将卵抗原呈递给来自感染的同基因对照小鼠的特异性致敏的CD 4（+）T辅助细胞。相比之下，来自MHC I类突变小鼠的细胞以与来自野生型对照的细胞相当的方式行使所有这些功能。这些观察结果清楚地表明，溶酶体虫卵肉芽肿是由MHC II类限制性CD 4（+）T辅助细胞介导的。他们还表明，CD 8（+）T细胞不会对虫卵抗原敏感，在血吸虫病的发病机制中几乎没有作用。
Previous studies have suggested that granulomatous inflammation in schistosomiasis is mediated by CD4(+) T helper lymphocytes sensitized to parasite egg antigens. However, CD8(+) T cells have also frequently been associated with the immune response to schistosome eggs. To examine more precisely the role of CD4(+) and CD8(+) T cells in the pathology of the schistosomal infection, we used mice with targeted mutations in major histocompatibility complex (MHC) class II or class I molecules. These mutations lead, respectively, to the virtual absence of CD4(+) and CD8(+) T cells. The results clearly show that schistosome-infected MHC class II mutant mice failed to form granulomas around parasite eggs. In contrast, infected MHC class I mutant mice displayed characteristic granulomatous lesions that were comparable to those in wild-type control mice. Moreover, lymphoid cells from MHC class IT mutant mice were unable to react to egg antigens with either proliferative or cytokine [interferon-gamma, interleukin (IL)-4, IL-10] responses; nor were they able to present egg antigens to specifically sensitized CD4(+) T helper cells from infected syngeneic control mice. By comparison, cells from MHC class I mutant mice exercised all these functions in a manner comparable with those from wild-type controls. These observations clearly demonstrate that schistosomal egg granulomas are mediated by MHC class II-restricted CD4(+) T helper cells. They also suggest that CD8(+) T cells do not become sensitized to egg antigens and play little role, if any, in the pathogenesis of schistosomiasis.