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Immunology ; 104(1): 92-8, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11576226

ABSTRACT

Mice lacking the suppressor of cytokine signalling-1 (SOCS1) die within weeks of birth with extensive fatty degeneration of the liver, consistent with acute hepatic toxicity to interferon-gamma (IFN-gamma), and inflammation of multiple organs. We show here that treatment for 1 week from birth with neutralizing antibody to IFN-gamma rescues SOCS1-/- mice from lethal liver disease but the mice subsequently succumb to chronic inflammatory lesions characterized by T-lymphocyte infiltration of skeletal muscle, pancreas, lung, liver and skin. Elevated blood levels of eosinophils, neutrophils and platelets were also observed and the thymic lymphocyte population was depleted of CD4+ CD8+ T cells and showed a reduced CD4 : CD8 ratio. All T-cell populations in thymus, spleen and lymph node exhibited an increased proportion of cells bearing the activation marker CD44. These data suggest an important role for SOCS1 in T-lymphocyte regulation.


Subject(s)
Carrier Proteins/immunology , Fatty Liver/prevention & control , Hepatitis, Animal/prevention & control , Inflammation/prevention & control , Interferon-gamma/antagonists & inhibitors , Animals , Animals, Newborn , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Carrier Proteins/genetics , Carrier Proteins/metabolism , Chronic Disease , Fatty Liver/immunology , Hepatitis, Animal/immunology , Inflammation/immunology , Inflammation/pathology , Interferon-gamma/immunology , Lymphocyte Count , Mice , Mice, Inbred C57BL , Mice, Mutant Strains , Repressor Proteins/genetics , Repressor Proteins/immunology , Repressor Proteins/metabolism , Suppressor of Cytokine Signaling 1 Protein , Suppressor of Cytokine Signaling Proteins , beta-Galactosidase/metabolism
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