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β7 整合素缺陷型小鼠的鼻腔免疫接种可保留增强的 IgA 免疫。

Nasal vaccination of β7 integrin-deficient mice retains elevated IgA immunity.

机构信息

Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Warmia and Mazury, Olsztyn, 10-718, Poland.

Department of Infectious Diseases & Immunology, College of Veterinary Medicine, University of Florida, Gainesville, FL, 32611-0880, USA.

出版信息

Immunol Cell Biol. 2020 Sep;98(8):667-681. doi: 10.1111/imcb.12364. Epub 2020 Jul 8.

Abstract

Understanding the migration of lymphocytes to nonintestinal mucosal sites is fundamental to developing mucosal vaccination strategies. Studies have shown that nasal and oral immunization with cholera toxin (CT) stimulates, in addition to α4β7 , the induction of αE (CD103)β7 B cells. To determine the extent to which αE-associated β7 contributes to antigen (Ag)-specific immunoglobulin (Ig)A responses in the upper respiratory tract, nasal CT vaccination was performed in wild-type (wt) and β7 mice. At 16 days postprimary immunization, upper respiratory tract IgA responses were greater in β7 mice than in wt mice. IgA induction by distal β7 Peyer's patches, mesenteric lymph nodes and small intestinal lamina propria was minimal, in contrast to elevated gut IgA responses in wt mice. By 42 days postprimary immunization, β7 gut IgA responses were restored, and upper respiratory tract Ag-specific IgA responses were equivalent to those of wt mice. Examination of homing receptor expression and cell-sorting experiments revealed that β7 mice have increased usage of β1 and αE integrins by upper respiratory tract B cells, suggesting that alternative integrins can facilitate lymphocyte migration to the upper respiratory tract, especially in the absence of β7.

摘要

了解淋巴细胞向非肠道黏膜部位的迁移对于开发黏膜疫苗接种策略至关重要。研究表明,用霍乱毒素(CT)进行鼻腔和口服免疫接种,除了刺激α4β7之外,还能诱导αE(CD103)β7 B 细胞。为了确定αE 相关的β7 在多大程度上有助于上呼吸道的抗原(Ag)特异性免疫球蛋白(Ig)A 反应,在野生型(wt)和β7 小鼠中进行了鼻腔 CT 疫苗接种。在初次免疫接种后 16 天,β7 小鼠的上呼吸道 IgA 反应大于 wt 小鼠。与 wt 小鼠的肠道 IgA 反应升高相比,远端 Peyer 斑、肠系膜淋巴结和小肠固有层的β7 Peyer 斑的 IgA 诱导作用最小。在初次免疫接种后 42 天,β7 肠道 IgA 反应得到恢复,上呼吸道 Ag 特异性 IgA 反应与 wt 小鼠相当。对归巢受体表达和细胞分选实验的检查表明,β7 小鼠的上呼吸道 B 细胞更多地使用β1 和 αE 整合素,这表明替代整合素可以促进淋巴细胞迁移至上呼吸道,特别是在缺乏β7 的情况下。

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