β2 integrins are required for skin homing of primed T cells but not for priming naive T cells
β2 integrins are required for skin homing of primed T cells but not for priming naive T cells
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DOI：
10.1172/jci11703
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发表时间：
2002-01-01
影响因子：
15.9
通讯作者：
Scharffetter-Kochanek, K
中科院分区：
文献类型：
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作者：
Grabbe, S;Varga, G;Scharffetter-Kochanek, K
β(2) 整合素对于白细胞通过血管内皮的外渗至关重要。以及T细胞激活。为了阐明2整合素在T细胞介导的免疫反应中的作用，在缺乏β(2)整合素亚基CD 18的小鼠中评估了过敏性接触性皮炎(ACD)、刺激性皮炎和迟发型超敏反应(DTH)。在CD18(-/-)小鼠中，ACD和DTH反应被严重抑制，但水肿形成未被抑制。 CD18(-/-) T细胞向湿疹皮损的外渗受到极大损害，而朗格汉斯细胞前体和树突状细胞的迁移在CD18(-/-)小鼠中是正常的。 CD18（-/-）淋巴结（LN）含有异常的CD3-CD44（高）淋巴细胞群，并显示出广泛T细胞激活的证据。来自致敏 CD18(-/-) 小鼠区域 LN 的 T 细胞响应半抗原攻击而增殖，并且将致敏同基因 LN 细胞直接皮下注射到半抗原攻击的幼稚受体的耳朵中恢复了 CD18(-/-) 小鼠中有缺陷的 ACD，表明 CD 18 不是幼稚 T 细胞的启动所必需的，但对于 T 细胞外渗是必不可少的。因此，除了粒细胞之外，T 细胞的功能障碍也可能导致 I 型白细胞粘附缺陷的病理生理学，这种缺陷是由人类 CD18 基因突变引起的。
beta(2) integrins are of critical importance for leukocyte extravasation through vascular endothelia. and for T cell activation. To elucidate the role Of 2 integrins in T cell-mediated immune responses, allergic contact dermatitis (ACD), irritant dermatitis, and delayed-type hypersensitivity (DTH) were assessed in mice lacking the beta(2) integrin subunit, CD 18. ACD and DTH responses, but not edema formation,were severely suppressed in CD18(-/-) mice. Extravasation of CD18(-/-) T cells into eczematous skin lesions was greatly impaired, whereas migration of Langerhans cell precursors and dendritic cells was normal in CD18(-/-)mice. CD18(-/-)Iymph nodes (LNs) contained an abnormal population of CD3-CD44(high) lymphocytes and showed evidence of widespread T cell activation. T cells from regional LNs of sensitized CD18(-/-) mice proliferated in response to hapten challenge, and subcutaneous injection of sensitized syngeneic LN cells directly into ears of hapten-challenged naive recipients restored the defective ACD in CD18(-/-) mice, suggesting that CD 18 is not required for priming of naive T cells but is indispensable for T cell extravasation. Thus, a dysfunction of T cells, in addition to granulocytes, may contribute to the pathophysicology of leukocyte adhesion deficiency type I, which arises from mutations in the human CD18 gene.