Graves' hyperthyroidism and the hygiene hypothesis in a mouse model.
Graves' hyperthyroidism is an organ-specific autoimmune disease mediated by stimulatory autoantibodies against the TSH receptor (TSHR; thyroid-stimulating antibodies), causing thyroid hyperplasia and hyperthyroidism. Development of this ailment is well known to be under polygenic and environmental control. For example, we recently demonstrated that parasite helminth Schistosoma mansoni infection suppressed a T helper cell type 1 (Th1)-type anti-TSHR immune response and prevented disease development in our mouse model of Graves' disease using adenovirus coding for the TSHR. In the present study we examined the outcome of infection with Mycobacterium bovis bacillus Calmette-Guerin (BCG), a Th1-promoting infectious pathogen, on Graves' disease. Our results show that prior infection with M. bovis BCG differentiates the TSHR-specific immune response toward a Th1 phenotype, as demonstrated by enhanced secretion of a Th1 cytokine interferon-gamma and impaired production of a Th2 cytokine IL-10 from splenocytes stimulated in vitro with TSHR antigen. M. bovis BCG also significantly suppressed disease induction. These data together with our recent report that coinjection of adenovirus expressing the Th1 cytokine IL-12 induced a Th1-polarized, TSHR-specific immune response without affecting disease development support the hygiene hypothesis, rather than Th1-mediated disease suppression. Thus, some infectious pathogens may influence the development of Graves' disease regardless of their ability to modify the Th1/Th2 balance.
Department of Medical Gene Technology, Atomic Bomb Disease Institute, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan. nagayama@net.nagasaki-u.ac.jp
Yuji
Y
Nagayama
Sandra M
SM
McLachlan
Basil
B
Rapoport
Kazunori
K
Oishi
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006111:Graves Disease / Q000276:immunology* / Q000628:therapy; D006920:Hygiene; D007165:Immunosuppression Therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D009163:Mycobacterium bovis; D018417:Th1 Cells / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology*