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表达Ag85B-IL-7融合蛋白的重组牛分枝杆菌卡介苗增强产生IL-17A的先天性γδT细胞。

Recombinant Mycobacterium bovis bacillus Calmette-Guérin expressing Ag85B-IL-7 fusion protein enhances IL-17A-producing innate γδ T cells.

作者信息

Hatano Shinya, Tamura Toshiki, Umemura Masayuki, Matsuzaki Goro, Ohara Naoya, Yoshikai Yasunobu

机构信息

Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, 3-1-1, Maidaishi, Higashi-ku, Fukuoka 812-8582, Japan.

Department of Microbiology, Leprosy Research Center, National Institute of Infectious Diseases, Tokyo 189-0002, Japan.

出版信息

Vaccine. 2016 May 11;34(22):2490-5. doi: 10.1016/j.vaccine.2016.03.096. Epub 2016 Apr 11.

DOI:10.1016/j.vaccine.2016.03.096
PMID:27079930
Abstract

Interleukin 7 (IL-7) has an important function in the development and maintenance of IL-17A+ γδ T cells. We here constructed a recombinant Mycobacterium bovis bacillus Calmette-Guérin expressing antigen 85B (Ag85B)-IL-7 fusion protein (rBCG-Ag85B-IL-7). The Ag85B-IL-7 fusion protein and IL-7 were detected in the bacterial lysate of rBCG-Ag85B-IL-7. rBCG-Ag85B-IL-7 was the same in number as control rBCG expressing Ag85B (rBCG-Ag85B) in the lung at the early stage after intravenous inoculation, whereas the numbers of IL-17A+ γδ T cells and Ag-specific Th1 cells were significantly higher in the lungs of mice inoculated with rBCG-Ag85B-IL-7 than those inoculated with rBCG-Ag85B. The Ag-specific Th1 cell response was impaired in mice lacking IL-17A+ γδ T cells after inoculation with rBCG-Ag85B-IL-7. Thus, rBCG-Ag85B-IL-7 increases the pool size of IL-17A+ γδ T cells, which subsequently augment the Th1 response to mycobacterial infection.

摘要

白细胞介素7(IL-7)在IL-17A+γδT细胞的发育和维持中具有重要作用。我们在此构建了一种表达抗原85B(Ag85B)-IL-7融合蛋白的重组牛分枝杆菌卡介苗(rBCG-Ag85B-IL-7)。在rBCG-Ag85B-IL-7的细菌裂解物中检测到了Ag85B-IL-7融合蛋白和IL-7。静脉接种后早期,rBCG-Ag85B-IL-7在肺中的数量与表达Ag85B的对照rBCG(rBCG-Ag85B)相同,然而,接种rBCG-Ag85B-IL-7的小鼠肺中IL-17A+γδT细胞和Ag特异性Th1细胞的数量显著高于接种rBCG-Ag85B的小鼠。接种rBCG-Ag85B-IL-7后,缺乏IL-17A+γδT细胞的小鼠中Ag特异性Th1细胞反应受损。因此,rBCG-Ag85B-IL-7增加了IL-17A+γδT细胞的库容量,随后增强了对分枝杆菌感染的Th1反应。

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