Treatment of autoimmune ovarian disease by co-administration with mouse zona pellucida protein 3 and DNA vaccine through induction of adaptive regulatory T cells

Authors

  • Jinyao Li,

    1. State Key Laboratory for Agro-Biotechnology, Department of Microbiology and Immunology, College of Biological Science, China Agricultural University, Beijing, China
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  • Huali Jin,

    1. State Key Laboratory for Agro-Biotechnology, Department of Microbiology and Immunology, College of Biological Science, China Agricultural University, Beijing, China
    2. Present address: Department of Microbiology and Immunology, College of Medicine, The University of Illinois at Chicago, Chicago, IL, USA
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  • Fuchun Zhang,

    1. Key Laboratory of Molecular Biology, College of Life Science and Technology, Xinjiang University, Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, Urumqi, China
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  • Xiaogang Du,

    1. State Key Laboratory for Agro-Biotechnology, Department of Microbiology and Immunology, College of Biological Science, China Agricultural University, Beijing, China
    2. Present address: Isotope Research Laboratory, College of Life and Physical Science, Sichuan Agricultural University, Ya'an, Sichuan, China
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  • Gan Zhao,

    1. State Key Laboratory for Agro-Biotechnology, Department of Microbiology and Immunology, College of Biological Science, China Agricultural University, Beijing, China
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  • Yang Yu,

    1. State Key Laboratory for Agro-Biotechnology, Department of Microbiology and Immunology, College of Biological Science, China Agricultural University, Beijing, China
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  • Bin Wang

    Corresponding author
    1. State Key Laboratory for Agro-Biotechnology, Department of Microbiology and Immunology, College of Biological Science, China Agricultural University, Beijing, China
    • State Key Laboratory for Agro-Biotechnology, China Agricultural University, Beijing 100094, China.
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Abstract

Background

Autoimmune ovarian disease (AOD) caused by auto-reactive T cells is considered a major reason for human premature ovarian failure, which affects 5% of women worldwide.

Methods and Results

To develop an effective treatment for AOD, we showed that the co-administration of mouse zona pellucida protein 3 (mZP3) protein and DNA vaccine encoding the mZP3 was able to meliorate AOD in an AOD murine model induced by the mZP3. We observed that established AOD in mice reverted to a normal ovarian morphology without notable T-cell infiltration in the co-administrated group; whereas mice in the control groups developed severe AOD. The amelioration appears to be antigen specific because other co-administration combinations failed to reverse AOD and correlates with significant reductions of pathogenic T-cell responses and productions of tumor necrosis factor-α and interferon-γ. Furthermore, the melioration is apparently associated with the induction of mZP3 specific regulatory T cells that exhibit a phenotypic CD4+CD25FoxP3+IL-10+ in the co-administrated group, which can be transferred to reverse AOD in vivo.

Conclusions

Thus, co-administration of mZP3 DNA and protein vaccines can be used to treat established AOD, and may provide a novel immunotherapy strategy to treat other autoimmune diseases. Copyright © 2008 John Wiley & Sons, Ltd.

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