Interleukin-4 protects against a genetically linked lupus-like autoimmune syndrome.
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.
Santiago
M L
ML
Institut National de la Santé et de la Recherche Médicale U 291, F-34197 Montpellier, France.
Fossati
L
L
Jacquet
C
C
Müller
W
W
Izui
S
S
Reininger
L
L
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis / Q000097:blood; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D004742:Enhancer Elements, Genetic; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007074:Immunoglobulin G / Q000097:blood; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics; D008181:Lupus Nephritis / Q000235:genetics* / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D013601:T-Lymphocytes / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology
D000974:Antibodies, Antinuclear; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D015847:Interleukin-4