Treatment of autoimmune ovarian disease by co-administration with mouse zona pellucida protein 3 and DNA vaccine through induction of adaptive regulatory T cells
Article first published online: 2 MAY 2008
Copyright © 2008 John Wiley & Sons, Ltd.
The Journal of Gene Medicine
Volume 10, Issue 7, pages 810–820, July 2008
How to Cite
Li, J., Jin, H., Zhang, F., Du, X., Zhao, G., Yu, Y. and Wang, B. (2008), Treatment of autoimmune ovarian disease by co-administration with mouse zona pellucida protein 3 and DNA vaccine through induction of adaptive regulatory T cells. J. Gene Med., 10: 810–820. doi: 10.1002/jgm.1200
- Issue published online: 16 JUN 2008
- Article first published online: 2 MAY 2008
- Manuscript Accepted: 26 MAR 2008
- Manuscript Revised: 17 MAR 2008
- Manuscript Received: 14 JAN 2008
- immune suppression;
- mZP3 protein;
- T regulatory cells
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+CD25−FoxP3+IL-10+ in the co-administrated group, which can be transferred to reverse AOD in vivo.
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.