Differential effects of interleukin-4 in peptide induced autoimmunity.
BALB/c mice immunized with multimeric DWEYSVWLSN develop IgG1 anti-DNA antibodies and glomerular immunoglobulin deposits, leading us to investigate the role of IL-4 in this model of antigen induced lupus. Splenocytes from DWEYSVWLSN immunized mice secreted IL-4 but not gamma-interferon. Following peptide immunization, IgG1 anti-peptide and anti-DNA antibodies were significantly higher in IL-4 wild type mice, while IgM and IgG3 anti-DNA levels were significantly higher in IL-4 knockout mice. Titers of IgG anti-laminin and anti-histone, but not anti-Sm/RNP and anti-cardiolipin antibodies, were significantly higher in the IL-4 wild type group. Glomerular immunoglobulin deposition was substantially decreased in IL-4 knockout mice. We conclude that while IL-4 does not materially affect the generation of some autoantibody responses associated with peptide induced autoimmunity, IL-4 deficiency inhibits kidney immunoglobulin deposition. The effect of IL-4 on humoral autoimmunity in lupus is complex, and is dependent on genetic background, the antigenic trigger and stage of disease.
Deocharan
Bisram
B
The Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Marambio
Paola
P
Edelman
Morris
M
Putterman
Chaim
C
D000818:Animals; D001323:Autoantibodies / Q000032:analysis / Q000097:blood; D015551:Autoimmunity; D002478:Cells, Cultured; D004247:DNA / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D006657:Histones / Q000276:immunology; D007074:Immunoglobulin G / Q000032:analysis / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007150:Immunohistochemistry; D015847:Interleukin-4 / Q000096:biosynthesis / Q000172:deficiency / Q000276:immunology*; D007678:Kidney Glomerulus / Q000276:immunology; D007797:Laminin / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000209:etiology / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010455:Peptides; D013154:Spleen / Q000166:cytology / Q000378:metabolism
D001323:Autoantibodies; D006657:Histones; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007797:Laminin; D010455:Peptides; D015847:Interleukin-4; D004247:DNA