The effects of a monoclonal antibody to interferon-gamma on experimental autoimmune thyroiditis (EAT): prevention of disease and decrease of EAT-specific T cells.
CBA/J mice immunized with thyroglobulin (Tg) develop an experimental autoimmune thyroiditis (EAT) with lymphocytic infiltration of the thyroid glands, autoantibodies to Tg and occurrence of EAT-specific T cells. When these mice were treated for 4 weeks after immunization with 1 mg/week of a monoclonal antibody (mAb) that neutralizes the activity of interferon-gamma (IFN) a beneficial effect on the onset of EAT was observed. Characteristic features of EAT were significantly reduced, including the lymphocytic infiltrations of the thyroid glands and the serum levels of autoantibodies to Tg. Moreover, in lymphoid organs, mAb to IFN-gamma significantly reduced the percentages of Tg-specific CD8+ cells, labeled by the anti-clonotypic mAb AG7. These Tg-specific T cells seem responsible for thyroid damages and disease development, since EAT was simultaneously abrogated. These results show that IFN-gamma plays an essential role in the pathophysiology of EAT and suggest the possibility to treat autoimmune thyroid diseases with mAb to IFN-gamma or drugs able to antagonize the production and/or the action of this cytokine.
Tang
H
H
Inserm U283, Unité de Recherches sur la Pathologie Autoimmune, Hopital Cochin, Paris.
Mignon-Godefroy
K
K
Meroni
P L
PL
Garotta
G
G
Charreire
J
J
Nicoletti
F
F
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D007114:Immunization; D007371:Interferon-gamma / Q000502:physiology*; D051379:Mice; D008808:Mice, Inbred CBA; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology*; D013954:Thyroglobulin / Q000276:immunology; D013967:Thyroiditis, Autoimmune / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*
D000911:Antibodies, Monoclonal; D007371:Interferon-gamma; D013954:Thyroglobulin