title: IL-28B down-regulates regulatory T cells but does not improve the protective immunity following tuberculosis subunit vaccine immunization.
abstract: Regulatory T cells (Tregs), which could be down-regulated by IL-28B, were reported to suppress T-cell-mediated immunity. The aim of this study was to investigate the role of IL-28B on the immune responses and protective efficacy of a tuberculosis (TB) subunit vaccine. First, a recombinant adenoviral vector expressing mouse IL-28B (rAd-mIL-28B) was constructed; then C57BL/6 mice were immunized with subunit vaccine ESAT6-Ag85B-Mpt64(190-198)-Mtb8.4-HspX (EAMMH) and rAd-mIL-28B together thrice or primed with Mycobacterium bovis bacillus Calmette-Gue'rin (BCG) and boosted by EAMMH and rAd-mIL-28B twice. At last the immune responses were evaluated, and the mice primed with BCG and boosted by subunit vaccines were challenged with virulent Mycobacterium tuberculosis H37Rv to evaluate the protective efficacy. The results showed that rAd-mIL-28B treatment significantly down-regulated the frequency of Tregs at 4 weeks after the last immunization but did not increase the Th1-type immune responses. Moreover, in the regimen of BCG priming and EAMMH boosting, rAd-mIL-28B treatment did not increase the antigen-specific cellular and humoral immune responses, and consequently did not reduce the bacteria load following H37Rv challenge. Instead, it induced more serious pathology reaction. In conclusion, IL-28B down-regulates Tregs following EAMMH vaccination but does not improve the protective immune responses.
authors.affiliation: Gansu Provincial Key Laboratory of Evidence Based Medicine and Clinical Translation & Lanzhou Center for Tuberculosis Research, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China Department of Immunology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Gansu Provincial Key Laboratory of Evidence Based Medicine and Clinical Translation & Lanzhou Center for Tuberculosis Research, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China Department of Immunology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China.
authors.forename: Xingming
authors.initials: X
authors.lastname: Ma
authors.affiliation: Gansu Provincial Key Laboratory of Evidence Based Medicine and Clinical Translation & Lanzhou Center for Tuberculosis Research, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China Institute of Pathogen Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Liu
authors.affiliation: Gansu Provincial Key Laboratory of Evidence Based Medicine and Clinical Translation & Lanzhou Center for Tuberculosis Research, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China Department of Immunology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Lu
authors.affiliation: Gansu Provincial Key Laboratory of Evidence Based Medicine and Clinical Translation & Lanzhou Center for Tuberculosis Research, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China Institute of Pathogen Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Niu
authors.affiliation: Gansu Provincial Key Laboratory of Evidence Based Medicine and Clinical Translation & Lanzhou Center for Tuberculosis Research, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China Department of Immunology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China.
authors.forename: Hongjuan
authors.initials: H
authors.lastname: Yu
authors.affiliation: Gansu Provincial Key Laboratory of Evidence Based Medicine and Clinical Translation & Lanzhou Center for Tuberculosis Research, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China Institute of Pathogen Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China.
authors.forename: Chunxiang
authors.initials: C
authors.lastname: Bai
authors.affiliation: Gansu Provincial Key Laboratory of Evidence Based Medicine and Clinical Translation & Lanzhou Center for Tuberculosis Research, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China Institute of Pathogen Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China.
authors.forename: Jinxiu
authors.initials: J
authors.lastname: Peng
authors.affiliation: ABSL-3 Lab, Wuhan University, Wuhan 430072, China.
authors.forename: Qiaoyang
authors.initials: Q
authors.lastname: Xian
authors.affiliation: ABSL-3 Lab, Wuhan University, Wuhan 430072, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Gansu Provincial Key Laboratory of Evidence Based Medicine and Clinical Translation & Lanzhou Center for Tuberculosis Research, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China Institute of Pathogen Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China bdzhu@lzu.edu.cn.
authors.forename: Bingdong
authors.initials: B
authors.lastname: Zhu
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D058491:Bacterial Load; D005260:Female; D006801:Humans; D007109:Immunity; D007372:Interferons / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000235:genetics / Q000276:immunology*; D022223:Vaccines, Subunit / Q000235:genetics / Q000276:immunology
chemical_list: D032581:Tuberculosis Vaccines; D022223:Vaccines, Subunit; C000602567:interferon-lambda3, mouse; D007372:Interferons
keywords: IL-28B; cytokine; immune regulation; regulatory T cells; tuberculosis vaccine