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Interleukin-4 protects against a genetically linked lupus-like autoimmune syndrome

Fossati-Jimack, Liliane
Jacquet, Chantal
Muller, W.
Reininger, Luc
Published in Journal of Experimental Medicine. 1997, vol. 185, no. 1, p. 65-70
Abstract Interleukin-4 (IL-4) provides support for humoral immune responses through upregulation of T helper (Th) type 2 cell differentiation, but it is not known whether IL-4 promotes antibody-mediated autoimmune diseases such as systemic lupus erythematosus (SLE). Here, we show that the constitutive expression of an IL-4 transgene by B cells completely prevents the development of lethal lupus-like glomerulonephritis in the (NZW x C57BL/6.Yaa)F1 murine model of SLE. This was associated with marked changes in the serum levels of IgG subclasses, rather than in the total levels of anti-DNA antibodies, with a lack of IgG3, a decrease of IgG2a, and an increase in IgG1 subclasses, and by a strong reduction in the serum levels of gp70-anti-gp70 immune complexes. This effect of the transgene appears to result from a modulation of the Th1 versus Th2 autoimmune response, since the protected mice displayed comparably modified IgG2a and IgG3 antibody response against exogenous T cell-dependent antigen, but not against T cell-independent antigens. Thus, IL-4 prevents the development of this lupus-like autoimmune disease, most likely by downregulating the appearance of Th1-mediated IgG subclasses of autoantibodies such as the IgG3 autoantibodies which have been shown to be especially nephritogenic.
Keywords AnimalsAntibodies, Antinuclear/biosynthesis/bloodAntibody FormationB-Lymphocytes/ immunologyCell DifferentiationEnhancer Elements, GeneticEnzyme-Linked Immunosorbent AssayFlow CytometryImmunoglobulin G/bloodImmunoglobulin Heavy Chains/geneticsInterleukin-4/ biosynthesis/geneticsLupus Nephritis/ genetics/immunology/ prevention & controlMiceMice, Inbred C57BLMice, Inbred StrainsMice, TransgenicPromoter Regions, GeneticT-Lymphocytes/immunologyTh2 Cells/cytology/immunology
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PMID: 8996242
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