Experimental autoimmune thyroiditis (EAT) in mice lacking the IFN-gamma receptor gene.
To investigate the role of interferon-gamma (IFN-gamma) in experimental autoimmune thyroidits (EAT), H-2k mice with a disrupted IFN-gamma receptor (IFN-gamma R) gene were immunized with porcine thyroglobulin (pTg). We observed that EAT occurred on day 19 and remitted on day 35 in IFN-gamma R-deficient (IFN-gamma R(0/0)) mice, whereas in wild-type mice, EAT occurred on day 21 and remitted on day 42-49. Moreover, EAT in the mutant mice was attenuated and accompanied by diminished Tg-specific cytotoxic and proliferative responses and decreased titers of anti-Tg antibodies, notably of the IgG2a and IgG2b isotypes. In contrast, Tg-specific IgG1 was increased in the IFN-gamma R(0/0) mice. In supernatants from T cells further stimulated in vitro by Tg, IFN-gamma levels were higher in IFN-gamma R(0/0) than in wild-type mice throughout the course of the disease, whereas interleukin-10 was transiently increased prior to EAT onset in both groups of mice. Finally, using IFN-gamma R(0/0) mice, we demonstrate that induction of EAT does not require an intact IFN-gamma system, while progression to full-blown disease depends on the action of IFN-gamma.
Alimi
E
E
INSERM U 283, Hôpital Cochin, Paris, France.
Huang
S
S
Brazillet
M P
MP
Charreire
J
J
D000276:Adjuvants, Immunologic; D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics*; D017077:Culture Media, Conditioned; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma / Q000502:physiology*; D016753:Interleukin-10 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000032:analysis / Q000378:metabolism; D051379:Mice; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D017471:Receptors, Interferon / Q000172:deficiency* / Q000235:genetics; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D013954:Thyroglobulin / Q000276:immunology; D013967:Thyroiditis, Autoimmune / Q000235:genetics*; D000096743:Interferon gamma Receptor
D000276:Adjuvants, Immunologic; D017077:Culture Media, Conditioned; D007074:Immunoglobulin G; D007371:Interferon-gamma; D016753:Interleukin-10; D008222:Lymphokines; D017471:Receptors, Interferon; D013954:Thyroglobulin; D000096743:Interferon gamma Receptor