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维生素A+D缺乏小鼠接种流感疫苗后气道淋巴细胞中CD103表达增强及病毒特异性CD8 T细胞频率降低

Enhanced CD103 Expression and Reduced Frequencies of Virus-Specific CD8 T Cells Among Airway Lymphocytes After Influenza Vaccination of Mice Deficient in Vitamins A + D.

作者信息

Surman Sherri L, Jones Bart G, Woodland David L, Hurwitz Julia L

机构信息

1 Department of Infectious Diseases, St. Jude Children's Research Hospital , Memphis, Tennessee.

2 Trudeau Institute , Saranac Lake, New York.

出版信息

Viral Immunol. 2017 Dec;30(10):737-743. doi: 10.1089/vim.2017.0086. Epub 2017 Nov 13.

Abstract

Previous research has evaluated antibody responses toward an influenza virus vaccine in the context of deficiencies for vitamins A and D (VAD+VDD). Results showed that antibodies and antibody-forming cells in the respiratory tract were reduced in VAD+VDD mice. However, effectors were recovered when oral supplements of vitamins A + D were delivered at the time of vaccination. Here we address the question of how vaccine-induced CD8 T cell responses are affected by deficiencies for vitamins A + D. VAD+VDD and control mice were vaccinated with an intranasal, cold-adapted influenza virus A/Puerto Rico/8/34 vaccine, with or without oral supplements of vitamins A + D. Results showed that the percentages of vaccine-induced CD8 T cell and total CD4 T cell responses were low among lymphocytes in the airways of VAD+VDD animals compared to controls. The CD103 membrane marker, a protein that binds e-cadherin (expressed on respiratory tract epithelial cells), was unusually high on virus-specific T cells in VAD+VDD mice compared to controls. Interestingly, when T cells specific for the PA/D epitope were compared with T cells specific for the NP/D epitope, the former population was more strongly positive for CD103. Preliminary experiments revealed normal or above-normal percentages for vaccine-induced T cells in airways when VAD+VDD animals were supplemented with vitamins A + D at the time of vaccination and on days 3 and 7 after vaccination. Our results suggest that close attention should be paid to levels of vitamins A and D among vaccine recipients in the clinical arena, as low vitamin levels may render individuals poorly responsive to vaccines.

摘要

先前的研究评估了维生素A和D缺乏(VAD+VDD)情况下对流感病毒疫苗的抗体反应。结果显示,VAD+VDD小鼠呼吸道中的抗体和抗体形成细胞减少。然而,在接种疫苗时口服补充维生素A+D后,效应细胞得以恢复。在此,我们探讨维生素A+D缺乏如何影响疫苗诱导的CD8 T细胞反应。VAD+VDD小鼠和对照小鼠接种了鼻内冷适应甲型流感病毒A/波多黎各/8/34疫苗,接种时或接种时及接种后第3天和第7天口服补充维生素A+D。结果显示,与对照组相比,VAD+VDD动物气道淋巴细胞中疫苗诱导的CD8 T细胞和总CD4 T细胞反应百分比很低。与对照组相比,VAD+VDD小鼠中病毒特异性T细胞上的CD103膜标记物(一种与E-钙黏蛋白结合的蛋白质,在呼吸道上皮细胞上表达)异常高。有趣的是,当比较PA/D表位特异性T细胞和NP/D表位特异性T细胞时,前一组CD103的阳性更强。初步实验表明,在接种疫苗时以及接种后第3天和第7天给VAD+VDD动物补充维生素A+D时,气道中疫苗诱导的T细胞百分比正常或高于正常。我们的结果表明,临床领域应密切关注疫苗接种者的维生素A和D水平,因为低维生素水平可能使个体对疫苗反应不佳。

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