Tolerogenic DNA vaccine for prevention of autoimmune ovarian disease.
DNA vaccines have been widely used to induce immune responses against molecular targets. In this study, we explored the possibility of using DNA vaccine combined with the immunosuppressant FK506 (tacrolimus) to antigen-specifically suppress unwanted immune responses and prevent autoimmune ovarian disease. To that end, we immunized C57BL/6 mice with a DNA vaccine encoding mouse zona pellucida 3 (ZP3) together with FK506. The immunization induced ZP3-specific CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg), which suppressed the induction of ZP3-specific delayed-type hypersensitivity in the animals. Significantly, the immunization also protected the animals from experimentally induced autoimmune ovarian disease. These results suggest that DNA vaccination in the presence of FK506 may be used to induce Treg cells and prevent AOD.
State Key Laboratory for Agro-Biotechnology, Key Laboratory of Microbiological Resources and Applications of the Ministry of Agriculture, College of Biological Science, China Agricultural University, Beijing 100193, China. kymin1012@163.com
Youmin
Y
Kang
Guoxing
G
Zheng
Aoshuang
A
Chen
Junpeng
J
Wang
Yanxin
Y
Hu
Jinyao
J
Li
Jingyao
J
Zhang
Wenjuan
W
Gao
Hongye
H
Fu
Guoliang
G
Xia
Bin
B
Wang
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000517:prevention & control*; D015704:CD4 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D004527:Egg Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006968:Hypersensitivity, Delayed / Q000139:chemically induced / Q000276:immunology* / Q000517:prevention & control; D007108:Immune Tolerance; D007114:Immunization; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010049:Ovarian Diseases / Q000276:immunology / Q000517:prevention & control*; D011956:Receptors, Cell Surface / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016559:Tacrolimus / Q000008:administration & dosage / Q000009:adverse effects; D019444:Vaccines, DNA / Q000008:administration & dosage*; D000072216:Zona Pellucida Glycoproteins
D015704:CD4 Antigens; D004527:Egg Proteins; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D019444:Vaccines, DNA; D000072216:Zona Pellucida Glycoproteins; C000606521:Zp3 protein, mouse; D016559:Tacrolimus