title: CD8+CD122+ T cells, a newly identified regulatory T subset, negatively regulate Graves' hyperthyroidism in a murine model.
abstract: Graves' disease is a thyroid-specific autoimmune disease mediated by stimulatory autoantibodies against the TSH receptor (TSHR). We have previously shown in our mouse model with adenovirus expressing the TSHR that antibody mediated depletion of CD4(+)CD25(+) regulatory T cells (Tregs) enhances incidence and severity of hyperthyroidism in resistant and susceptible mouse strains, respectively. These data indicate that balance between effector T cells and Tregs is critical for disease development. This study was designed to evaluate the role played by another recently identified type of Treg, CD8(+)CD122(+) T cells, in our mouse model to delineate the significance of different types of Tregs in Graves' disease. Flow cytometry analysis showed that CD4(+)CD25(+) and CD8(+)CD122(+) T cells are distinct cell types, and anti-CD122 antibody effectively and selectively depleted CD8(+)CD122(+) T cells. As for CD4(+)CD25(+) Treg, CD8(+)CD122(+) T cell depletion increased the incidence of hyperthyroidism both in resistant and susceptible mice. Of interest, intrathyroidal lymphocytic infiltration was observed in some CD8(+)CD122(+) T cell-depleted, hyperthyroid resistant mice. These results indicate that in addition to CD4(+)CD25(+) T cells, CD8(+)CD122(+) T cells also play a crucial role in disease susceptibility in mouse Graves' disease. Thus, different types of Tregs appear to be involved in tolerance to a self-antigen, the TSHR.
authors.affiliation: Department of Medical Gene Technology, Atomic Bomb Disease Institute, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, Japan.
authors.forename: Ohki
authors.initials: O
authors.lastname: Saitoh
authors.forename: Norio
authors.initials: N
authors.lastname: Abiru
authors.forename: Mami
authors.initials: M
authors.lastname: Nakahara
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nagayama
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015704:CD4 Antigens / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D006111:Graves Disease / Q000097:blood / Q000276:immunology*; D006980:Hyperthyroidism / Q000097:blood / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D053646:Interleukin-2 Receptor beta Subunit / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011989:Receptors, Thyrotropin / Q000276:immunology; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013963:Thyroid Hormones / Q000097:blood / Q000378:metabolism