Fucosyltransferase VII-deficient mice with defective E-, P-, and L-selectin ligands show impaired CD4+ and CD8+ T cell migration into the skin, but normal extravasation into visceral organs

Fucosyltransferase VII-deficient mice with defective E-, P-, and L-selectin ligands show impaired CD4+ and CD8+ T cell migration into the skin, but normal extravasation into visceral organs
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DOI:
10.4049/jimmunol.168.5.2139
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发表时间:
2002-03-01
影响因子:
4.4
通讯作者:
Kündig, TM
Kündig, TM
中科院分区:
医学2区
文献类型:
--
作者:
Erdmann, I;Scheidegger, EP;Kündig, TM

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白细胞外渗的第一步,白细胞滚动,是由E-,P-和L-选择素介导的。缺乏α-1,3-岩藻糖基转移酶VII(FucTVII)(-/-)的小鼠的特征在于缺乏E-、P-和L-选择素配体活性。该模型系统用于评估选择素与其配体在T和B细胞应答中的相互作用的作用。在本研究中,FucTVII(-/-)小鼠显示耳朵对FITC的CD 4(+)T细胞介导的接触性超敏反应降低,以及脚垫对淋巴细胞性脉络丛脑膜炎病毒感染的CD 8(+)T细胞介导的迟发型超敏反应降低。由于发现朗格汉斯细胞迁移至局部淋巴结以及CD 4(+)和CD 8(+)T细胞诱导正常,因此这些反应的传入臂未受损。皮肤炎症反应的减少是由于淋巴细胞外渗到皮肤中的效率低下。相比之下,在FucTVII(-/-)小鼠中,CD 4(+)和CD 8(+)T细胞外渗到内脏器官(如卵巢或大脑)中并未受损。从卵巢和脑中消除牛痘病毒和淋巴细胞性脉络丛脑膜炎病毒,以及从几个内脏器官中消除肿瘤细胞是正常的。因此,选择素与其配体的相互作用对于淋巴细胞归巢到皮肤中很重要,但对于淋巴细胞溢出到内脏器官中不重要。
The first step of leukocyte extravasation, leukocyte rolling, is mediated by E-, P-, and L-selectins. Mice deficient for alpha-1,3-fucosyltransferase VII (FucTVII)(-/-) are characterized by deficiency of E-, P-, and L-selectin ligand activity. This model system was used to evaluate the role of the interactions of selectins with their ligands in T and B cell responses. In the present study, FucTVII(-/-) mice showed reduced CD4(+) T cell-mediated contact hypersensitivity reactions of the ears to FITC as well as reduced CD8(+) T cell-mediated delayed-type hypersensitivity reactions of the footpads against lymphocytic choriomeningitis virus infection. As Langerhans cell migration to local lymph nodes as well as CD4(+) and CD8(+) T cell induction were found to be normal, the afferent arm of these reactions was not impaired. The reduced inflammatory reactions of the skin were due to inefficient lymphocyte extravasation into the skin. In contrast, extravasation of CD4(+) and CD8(+) T cells into visceral organs, such as the ovaries or the brain, was not impaired in FucTVII(-/-) mice. Elimination of vaccinia virus and of lymphocytic choriomeningitis virus from ovaries and brain, as well as elimination of tumor cells from several visceral organs was normal. Thus, interactions of selectins with their ligands are important for lymphocyte homing into the skin, but not for lymphocyte extravasation into visceral organs.