Induction of granulomatous experimental autoimmune thyroiditis in mice with in vitro activated effector T cells and anti-IFN-gamma antibody.
Experimental autoimmune thyroiditis (EAT) can be induced in mice after the transfer of mouse thyroglobulin (MTg)-sensitized donor spleen cells that have been activated in vitro with MTg. CD4+ T cells are required for the transfer of EAT in this model. Because CD4+ T cells produce various lymphokines, such as IFN-gamma, that may be involved in the activation or regulation of the immune response to MTg and the development of EAT, the present study was undertaken to determine whether a neutralizing mAb to IFN-gamma could modulate the induction or expression of EAT. The anti-IFN-gamma mAb XMG-1.2 had no effect on sensitization of donor cells. However, addition of XMG-1.2 mAb during in vitro activation of MTg-primed spleen cells resulted in more severe EAT in recipient mice. The thyroid lesions in recipients of cells cultured with MTg and XMG-1.2 mAb also exhibited granulomatous changes, which differed qualitatively from the predominantly lymphocytic cell infiltrates in recipients of cells cultured with MTg alone. Recipients of MTg-activated spleen cells also developed severe granulomatous EAT when they were given injections of XMG-1.2 mAb. The effects of XMG-1.2 could be neutralized by IFN-gamma. Recipients of cells cultured in the presence of XMG-1.2 mAb had augmented autoantibody responses, although there were no apparent differences in the IgG subclass distribution of the anti-MTg autoantibody responses. These studies suggest that neutralization of endogenous IFN-gamma results in increased activity of cells capable of inducing granulomatous EAT in mice.
Stull
S J
SJ
Department of Medicine, University of Missouri, Columbia 65212.
Sharp
G C
GC
Kyriakos
M
M
Bickel
J T
JT
Braley-Mullen
H
H
D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D006099:Granuloma / Q000276:immunology; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma / Q000502:physiology*; D008213:Lymphocyte Activation; D051379:Mice; D008808:Mice, Inbred CBA; D013601:T-Lymphocytes / Q000276:immunology*; D013954:Thyroglobulin / Q000276:immunology; D013967:Thyroiditis, Autoimmune / Q000276:immunology*; D013997:Time Factors
D001323:Autoantibodies; D007074:Immunoglobulin G; D007371:Interferon-gamma; D013954:Thyroglobulin