title: Suppression of autoimmune neuritis in IFN-gamma receptor-deficient mice.
abstract: 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.
authors.affiliation: Division of Geriatric Medicine, Department of Clinical Neuroscience, Karolinska Institute, Huddinge University Hospital, S-141 86 Stockholm, Sweden.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhu
authors.forename: H G
authors.initials: HG
authors.lastname: Ljunggren
authors.forename: E
authors.initials: E
authors.lastname: Mix
authors.forename: H L
authors.initials: HL
authors.lastname: Li
authors.forename: P
authors.initials: P
authors.lastname: van der Meide
authors.forename: A M
authors.initials: AM
authors.lastname: Elhassan
authors.forename: B
authors.initials: B
authors.lastname: Winblad
authors.forename: J
authors.initials: J
authors.lastname: Zhu
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D018450:Disease Progression; D005246:Feedback; D005620:Freund's Adjuvant; D006801:Humans; D007249:Inflammation; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology / Q000473:pathology; D018993:Myelin P0 Protein / Q000276:immunology; D009444:Neuritis, Autoimmune, Experimental / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology*; D010446:Peptide Fragments / Q000276:immunology; D017471:Receptors, Interferon / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012584:Sciatic Nerve / Q000276:immunology* / Q000473:pathology; D000096743:Interferon gamma Receptor
chemical_list: D005620:Freund's Adjuvant; D007371:Interferon-gamma; D018664:Interleukin-12; D015847:Interleukin-4; D018993:Myelin P0 Protein; D010446:Peptide Fragments; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor