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


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-alpha and interferon-gamma. 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.


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.
Li
Jinyao
J
Department of Microbiology and Immunology, State Key Laboratory for Agro-Biotechnology, College of Biological Science, China Agricultural University, Beijing, China.
Jin
Huali
H
Zhang
Fuchun
F
Du
Xiaogang
X
Zhao
Gan
G
Yu
Yang
Y
Wang
Bin
B
D000818:Animals; D000911:Antibodies, Monoclonal; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology; D049109:Cell Proliferation; D017931:DNA Primers / Q000235:genetics; D004527:Egg Proteins / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005434:Flow Cytometry; D007167:Immunotherapy / Q000379:methods*; D008562:Membrane Glycoproteins / Q000008:administration & dosage / Q000627:therapeutic use*; D051379:Mice; D010049:Ovarian Diseases / Q000188:drug therapy* / Q000276:immunology; D011956:Receptors, Cell Surface / Q000008:administration & dosage / Q000627:therapeutic use*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology / Q000627:therapeutic use*; D000072216:Zona Pellucida Glycoproteins
D000911:Antibodies, Monoclonal; D017931:DNA Primers; D004527:Egg Proteins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D019444:Vaccines, DNA; D000072216:Zona Pellucida Glycoproteins