Suppression of autoimmune neuritis in IFN-gamma receptor-deficient mice
Autor(es): Zhu Y,Ljunggren H G,Mix E,Li H L,van der Meide P,Elhassan A M,Winblad B,Zhu J
Resumo: Experimental autoimmune neuritis (EAN) is an animal model of the human disease Guillain-Barré syndrome. In this autoimmune inflammatory disease, CD4(+) T cells mediate demyelination in the peripheral nervous system (PNS). Infiltrating macrophages and T cells as well as cytokines like interferon (IFN)-gamma are intimately involved in causing pathogenic effects. To investigate the role of IFN-gamma in cell-mediated EAN, IFN-gamma receptor-deficient mutant (IFN-gammaR(-/-)) C57BL/6 mice and corresponding wild-type mice were immunized with P0 peptide 180-199, a purified component of peripheral nerve myelin, and Freund's complete adjuvant. IFN-gammaR(-/-) mice exhibited later onset of clinical disease. The disease was also less severe than in wild-type mice. Fewer IL-12-producing but more IL-4-producing cells were found in sciatic nerve sections from IFN-gammaR(-/-) mice than from wild-type mice on day 24 postimmunization, i.e., at the peak of clinical EAN. At the same time, IFN-gammaR(-/-) mice had less infiltration of inflammatory cells, including macrophages, CD4(+) T cells, and monocytes, into sciatic nerve tissue and less demyelination. However, numbers of IFN-gamma-secreting cells from the spleen were significantly augmented in the IFN-gammaR(-/-) mice, reflecting a failure of negative feedback circuits. The IFN-gammaR deficiency did not affect the production of anti-P0 peptide 180-199-specific antibodies. These results indicate that IFN-gamma contributes to a susceptibility for EAN in C57BL/6 mice by promoting a Th1 cell-mediated immune response and suppressing a Th2 response.
Palavras-Chave: Experimental autoimmune neuritis; IFN-? receptor-deficient mice; Guillain-Barré syndrome; Th1/Th2 cytokine
Imprenta: Experimental Neurology, v. 169, n. 2, p. 472-478, 2001
Identificador do objeto digital: 10.1006/exnr.2001.7662
Descritores: Guillain-Barre Syndrome - Biosynthesis ; Guillain-Barre Syndrome - Cell ; Guillain-Barre Syndrome - Cytopathology ; Guillain-Barre Syndrome - Pathogenesis ; Guillain-Barre Syndrome - Protein synthesis ; Guillain-Barre Syndrome - Proteins ; Guillain-Barre Syndrome - Antibodies ; Guillain-Barre Syndrome - Cytokines ; Guillain-Barre Syndrome - Immune response ; Guillain-Barre Syndrome - Inflammation ; Guillain-Barre Syndrome - Immunology
Data de publicação: 2001
