IL-17作为分子佐剂增强蛋白疫苗细胞免疫应答的研究

中国生物工程杂志

2011, Vol. 31

Issue (7): 20-26

研究报告

IL-17作为分子佐剂增强蛋白疫苗细胞免疫应答的研究

楼曜宪¹, 邹强², 靳津², 王宪政², 张一帜², 王宾²

1. 中国农业大学动物医学院北京 100193;
2. 中国农业大学农业与生物技术国家重点实验室北京 100193

IL-17 as an Adjuvant Enhances Immune Responses of Recombinant Protein Vaccine

LOU Yao-xian¹, ZOU Qiang², JIN Jin², WANG Xian-zheng², ZHANG Yi-zhi², WANG Bin²

1. College of Veterinary Medicine, China Agricultural University, Beijing 100193, China;
2. State Key Laboratory for Agro-Biotechnology, College of Biological Science, China Agricultural University, Beijing 100193, China

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摘要：

目的:为了进一步增强重组蛋白质疫苗的细胞免疫应答,利用重组的IL-17作为分子佐剂,与卵清蛋白(ovalbumin,OVA)一起免疫小鼠, 研究IL-17作为分子佐剂对适应性免疫的影响,探索IL-17对蛋白疫苗诱导的免疫反应,特别是细胞免疫应答的影响。方法: 用OVA作为特异性蛋白疫苗,与不同剂量的IL-17联合免疫C57BL/6小鼠; 分别在第0, 2周进行免疫,在第3,4周分别检测抗-OVA IgG水平,T淋巴细胞增殖能力, 细胞因子表达水平和体内细胞毒性T淋巴细胞(cytotoxic T lymphocyte,CTL)杀伤作用等免疫学指标。结果: 以OVA作为的蛋白疫苗在IL-17作为佐剂情况下能够增强抗原特异性的免疫反应,尤其是有效提高细胞免疫应答水平。与单注射OVA蛋白组相比,不同剂量的IL-17不仅增强了OVA特异性抗体水平,而且均能够增强CD⁺₄T和CD⁺₈T细胞分泌IL-17的能力,尤其对CD⁺₈T细胞分泌IFN-γ的表达水平和体内CTL的效果增加明显。结论: IL-17作为蛋白质疫苗的分子佐剂能够增强抗体水平,特异性CD⁺₈T细胞活性, 尤其是增强体内特异性的CTL反应,这为增强蛋白质疫苗的特异性细胞免疫反应提供了一个新方法。

关键词： IL-17; 分子佐剂; OVA; 蛋白疫苗; 细胞免疫应答

Abstract:

Objective: To enhance immune responses to protein vaccine, IL-17 was investigated as a molecular adjuvant to enhance humoral immune responses, especially cellular immune responses to protein vaccine. Methods: C57BL/6 mice were immunized with OVA alone, or with IL-17A by intramuscular injection. The immunization was performed on week 0, 2. The concentration of the anti-OVA IgG, the stimulated index of T lymphocyte proliferation, and the expressions of IFN-γ, IL-4 and IL-17 in CD⁺₄ T cells and IL-17, IFN-γ in CD⁺₈ T cells, and specific in vivo cytotoxic T lymphocyte (CTL) activity were detected on week 3,4. Results: The results showed that IL-17 as a molecular adjuvant for the protein vaccine, OVA, could enhance immune responses, especially the cellular immune responses. IL-17 could not only enhance the humoral responses and T cell proliferation, but also the expressions of IL-17 in CD⁺₄ and CD⁺₈ T cells, and IFN-γ in CD⁺₈ T cells. Accordingly, the level of CTL in vivo was significantly increased. Conclusion: The results demonstrated that IL-17 as a molecular adjuvant enhanced humoral and cellular immune responses to protein vaccine, especially the CD⁺₈ T cell-immunity. The novel functionality of IL-17 on adaptive immunity may lead to develop new protein vaccine targeted to the cellular immune responses.

Key words: IL-17 Molecular adjuvant OVA Protein vaccine Cellular immune responses

收稿日期: 2011-03-31 出版日期: 2011-07-25

ZTFLH:

Q78

基金资助:

农业部转基因生物新品种培育科技重大专项(2008ZX08006-001)、吉林省博士后科研启动基金(00220)、吉林省农业科学院引进人才基金(00109)资助项目

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引用本文:

楼曜宪, 邹强, 靳津, 王宪政, 张一帜, 王宾. IL-17作为分子佐剂增强蛋白疫苗细胞免疫应答的研究[J]. 中国生物工程杂志, 2011, 31(7): 20-26.

LOU Yao-xian, ZOU Qiang, JIN Jin, WANG Xian-zheng, ZHANG Yi-zhi, WANG Bin. IL-17 as an Adjuvant Enhances Immune Responses of Recombinant Protein Vaccine. China Biotechnology, 2011, 31(7): 20-26.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/ 或 https://manu60.magtech.com.cn/biotech/CN/Y2011/V31/I7/20

[1] Dzierzbicka K, Kolodziejczyk A M. Adjuvants--essential components of new generation vaccines. Postepy Biochem, 2006,52(2):204-211.

[2] Korn T, Bettelli E, Oukka M, et al. IL-17 and Th17 Cells. Annu Rev Immunol, 2009,27(1): 485-517.

[3] Murugaiyan G, Mittal A, Weiner H L. Increased osteopontin expression in dendritic cells amplifies IL-17 production by CD⁺₄ T cells in experimental autoimmune encephalomyelitis and in multiple sclerosis. J Immunol, 2008, 181(11): 7480-7488.

[4] Wong C K, Lit L C, Tam L S, et al. Hyperproduction of IL-23 and IL-17 in patients with systemic lupus erythematosus: implications for Th17-mediated inflammation in auto-immunity. Clin Immunol, 2008,127( 3): 385-393.

[5] Kehlen A, Thiele K, Riemann D, et al. Expression, modulation and signalling of IL-17 receptor in fibroblast-like synoviocytes of patients with rheumatoid arthritis. Clin Exp Immunol, 2002,127(3): 539-546.

[6] 张景熙. IL-17与疾病相关的研究进展. 国外医学, 2004,27(1): 52-55. Zhang J X. Foreign Medical Sciences, 2004,27(1): 52-55.

[7] 秦霞, 刘钟滨. 白细胞介素17家族. 同济大学学报(医学版), 2003, 24(6): 519-522. Qin X, Liu Z B. Journal of Tongji University (Medical Science), 2003, 24(6): 519-522.

[8] Garley M, Jablonska E, Grabowska S Z, et al. IL-17 family cytokines in neutrophils of patients with oral epithelial squamous cell carcinoma. Neoplasma, 2009,56(2): 96-100.

[9] Arican O, Aral M, Sasmaz S, et al. Serum levels of TNF-alpha, IFN-gamma, IL-6, IL-8, IL-12, IL-17, and IL-18 in patients with active psoriasis and correlation with disease severity. Mediators Inflamm, 2005,2005(5): 273-279.

[10] Ma D, Zhu X, Zhao P, et al. Profile of Th17 cytokines (IL-17, TGF-beta, IL-6) and Th1 cytokine (IFN-gamma) in patients with immune thrombocytopenic purpura. Ann Hematol, 2008,87(11): 899-904.

[11] Mitsdoerffer M, Lee Y, Kuchroo V K, et al. Proinflammatory T helper type 17 cells are effective B-cell helpers. Proc Natl Acad Sci USA, 2010,107(32):14292-14297.

[12] Awasthi A, Kuchroo V K. IL-17A directly inhibits TH1 cells and thereby suppresses development of intestinal inflammation. Nat Immunol, 2009, 10(6): 568-570.

[13] Lindblad E B. Aluminium adjuvants-in retrospect and prospect. Vaccine,2004, 22(27-28):3658-3668.

[14] Da-Silva C A, Hartl D, Liu W, et al.TLR-2 and IL-17A in chitin-induced macrophage activation and acute inflammation. The Journal of Immunology, 2008,181(6): 4279-4286.

[15] Doreau A, Belot A, Bastid J, et al. Interleukin 17 acts in synergy with B cell-activating factor to influence B cell biology and the pathophysiology of systemic lupus erythematosus. Nat Immunol, 2009,10(7):778-785.

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