title: Induction of murine neonatal tolerance against Graves' disease using recombinant adenovirus expressing the TSH receptor A-subunit.
abstract: Graves' disease is a common organ-specific autoimmune disease. The identity of its autoantigen, the TSH receptor (TSHR), was established and used to induce a typical animal model. A-subunit, the shed portion of TSHR, either initiates or amplifies the autoimmune response of the thyroid gland, thereby causing Graves' disease in humans. In the present study, we investigate the effect of the TSHR A-subunit on the induction of murine neonatal tolerance for the development of Graves' disease. Female BALB/c mice were pretreated with different doses of adenovirus expressing the A-subunit of TSHR (Ad-TSHR289) by either ip or im injection within the first 24 h after their birth. Graves' disease was induced after the animals reached adulthood. Nearly all mice pretreated with the high dose of Ad-TSHR289 failed to develop TSHR antibodies, detected by the TSH-binding inhibition assay, hyperthyroidism, and thyroid follicular hyperplasia. The mice preimmunized im with the lower doses of Ad-TSHR289 developed a relatively low level of TSH-binding inhibition and the low incidence of hyperthyroidism. Accordingly, the percentages of splenic CD4+CD25+/CD4+ and CD25+Foxp3+/CD4+ Treg cells were increased in mice pretreated with the high dose of Ad-TSHR289. Taken together, our data strongly indicate that the immunotolerance against Graves' disease could be induced in neonatal mice using a specific TSHR antigen in a high dose either by ip or im injection, preventing the development of Graves' disease.
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University School of Medicine, 277 Yanta West Road, Shaanxi, Xi'an 710061, People's Republic of China.
authors.forename: Liping
authors.initials: L
authors.lastname: Wu
authors.forename: Liru
authors.initials: L
authors.lastname: Xun
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.forename: Li
authors.initials: L
authors.lastname: Xu
authors.forename: Zhufang
authors.initials: Z
authors.lastname: Tian
authors.forename: Shan
authors.initials: S
authors.lastname: Gao
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Peng
authors.initials: P
authors.lastname: Hou
authors.forename: Bingyin
authors.initials: B
authors.lastname: Shi
mesh_terms: D000256:Adenoviridae; D000818:Animals; D000906:Antibodies / Q000097:blood; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D015292:Glycoprotein Hormones, alpha Subunit / Q000235:genetics* / Q000378:metabolism*; D006111:Graves Disease / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000166:cytology; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism; D013974:Thyroxine / Q000097:blood
chemical_list: D000906:Antibodies; D015703:Antigens, CD; D015292:Glycoprotein Hormones, alpha Subunit; D013974:Thyroxine