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From * The Malaghan Institute of Medical Research and the Department of Medicine, Wellington
School of Medicine, Wellington South, New Zealand; The transgenic (tg) expression of interleukin (IL)-4 under the control of a major histocompatibility complex (MHC) class I promoter leads to B cell hyperactivity in mice, characterized by
increased B cell surface MHC class II and CD23 expression, elevated responsiveness of the B
cells to polyclonal ex vivo stimulation, and increased immunoglobulin (Ig)G1 and IgE serum
levels. Tg mice develop anemia, glomerulonephritis with complement and immune deposition
in the glomeruli, and show increased production of autoantibodies. Treatment of IL-4 tg mice
with anti-IL-4 neutralizing antibodies protected the mice from disease development, showing that IL-4 was responsible for the observed disorders. Deletion of superantigen responsive autoreactive T cells in the IL-4 tg mice was normal and treatment of mutant mice with deleting
anti-CD4 antibodies failed to ablate the onset of autoimmune-like disease, suggesting that
CD4+T cells were not the primary cause of the disorders. Furthermore, the deletion of B cells
reacting against MHC class I molecules was also normal in the IL-4 tg mice. Therefore the
most likely explanation for the increased production of autoantibodies and the autoimmunelike disorders is that IL-4 acts directly on autoreactive B cells by expanding them in a polyclonal manner. Taken together our results show that inappropriate multi-organ expression of IL-4 in vivo leads to autoimmune-type disease in mice.
Institut für Virologie und Immunbiologie der
Universität Würzburg, D-97070 Würzburg, Germany; and § Swiss Institute of Technology, Institute of
Toxicology, CH-8603 Schwerzenbach, Switzerland
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