Mice with IFN-gamma receptor deficiency are less susceptible to experimental autoimmune myasthenia gravis.
J Immunol
; 162(7): 3775-81, 1999 Apr 01.
Article
en En
| MEDLINE
| ID: mdl-10201893
IFN-gamma can either adversely or beneficially affect certain experimental autoimmune diseases. To study the role of IFN-gamma in the autoantibody-mediated experimental autoimmune myasthenia gravis (EAMG), an animal model of myasthenia gravis in humans, IFN-gammaR-deficient (IFN-gammaR-/-) mutant C57BL/6 mice and congenic wild-type mice were immunized with Torpedo acetylcholine receptor (AChR) plus CFA. IFN-gammaR-/- mice exhibited significantly lower incidence and severity of muscle weakness, lower anti-AChR IgG Ab levels, and lower Ab affinity to AChR compared with wild-type mice. Passive transfer of serum from IFN-gammaR-/- mice induced less muscular weakness compared with serum from wild-type mice. In contrast, numbers of lymph node cells secreting IFN-gamma and of those expressing IFN-gamma mRNA were strongly augmented in the IFN-gammaR-/- mice, reflecting a failure of negative feedback circuits. Cytokine studies by in situ hybridization revealed lower levels of lymphoid cells expressing AChR-reactive IL-1beta and TNF-alpha mRNA in AChR + CFA-immunized IFN-gammaR-/- mice compared with wild-type mice. No differences were found for AChR-reactive cells expressing IL-4, IL-10, or TGF-beta mRNA. These results indicate that IFN-gamma promotes systemic humoral responses in EAMG by up-regulating the production and the affinity of anti-AChR autoantibodies, thereby contributing to susceptibility to EAMG in C57BL/6-type mice.
Buscar en Google
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Interferón gamma
/
Receptores de Interferón
/
Predisposición Genética a la Enfermedad
/
Miastenia Gravis
Límite:
Animals
Idioma:
En
Revista:
J Immunol
Año:
1999
Tipo del documento:
Article
País de afiliación:
Suecia
Pais de publicación:
Estados Unidos