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.
Skip Nav Destination
Article navigation
20 January 1997
Article|
January 20 1997
Constitutive Expression of Interleukin (IL)-4 In Vivo Causes Autoimmune-type Disorders in Mice
Klaus J. Erb,
Klaus J. Erb
From *The Malaghan Institute of Medical Research and the Department of Medicine, Wellington School of Medicine, Wellington South, New Zealand; ‡Institut für Virologie und Immunbiologie der Universität Würzburg, D-97070 Würzburg, Germany; and §Swiss Institute of Technology, Institute of Toxicology, CH-8603 Schwerzenbach, Switzerland
Search for other works by this author on:
Beate Rüger,
Beate Rüger
From *The Malaghan Institute of Medical Research and the Department of Medicine, Wellington School of Medicine, Wellington South, New Zealand; ‡Institut für Virologie und Immunbiologie der Universität Würzburg, D-97070 Würzburg, Germany; and §Swiss Institute of Technology, Institute of Toxicology, CH-8603 Schwerzenbach, Switzerland
Search for other works by this author on:
Maja von Brevern,
Maja von Brevern
From *The Malaghan Institute of Medical Research and the Department of Medicine, Wellington School of Medicine, Wellington South, New Zealand; ‡Institut für Virologie und Immunbiologie der Universität Würzburg, D-97070 Würzburg, Germany; and §Swiss Institute of Technology, Institute of Toxicology, CH-8603 Schwerzenbach, Switzerland
Search for other works by this author on:
Bernhard Ryffel,
Bernhard Ryffel
From *The Malaghan Institute of Medical Research and the Department of Medicine, Wellington School of Medicine, Wellington South, New Zealand; ‡Institut für Virologie und Immunbiologie der Universität Würzburg, D-97070 Würzburg, Germany; and §Swiss Institute of Technology, Institute of Toxicology, CH-8603 Schwerzenbach, Switzerland
Search for other works by this author on:
Annelise Schimpl,
Annelise Schimpl
From *The Malaghan Institute of Medical Research and the Department of Medicine, Wellington School of Medicine, Wellington South, New Zealand; ‡Institut für Virologie und Immunbiologie der Universität Würzburg, D-97070 Würzburg, Germany; and §Swiss Institute of Technology, Institute of Toxicology, CH-8603 Schwerzenbach, Switzerland
Search for other works by this author on:
Karen Rivett
Karen Rivett
From *The Malaghan Institute of Medical Research and the Department of Medicine, Wellington School of Medicine, Wellington South, New Zealand; ‡Institut für Virologie und Immunbiologie der Universität Würzburg, D-97070 Würzburg, Germany; and §Swiss Institute of Technology, Institute of Toxicology, CH-8603 Schwerzenbach, Switzerland
Search for other works by this author on:
Klaus J. Erb
From *The Malaghan Institute of Medical Research and the Department of Medicine, Wellington School of Medicine, Wellington South, New Zealand; ‡Institut für Virologie und Immunbiologie der Universität Würzburg, D-97070 Würzburg, Germany; and §Swiss Institute of Technology, Institute of Toxicology, CH-8603 Schwerzenbach, Switzerland
Beate Rüger
From *The Malaghan Institute of Medical Research and the Department of Medicine, Wellington School of Medicine, Wellington South, New Zealand; ‡Institut für Virologie und Immunbiologie der Universität Würzburg, D-97070 Würzburg, Germany; and §Swiss Institute of Technology, Institute of Toxicology, CH-8603 Schwerzenbach, Switzerland
Maja von Brevern
From *The Malaghan Institute of Medical Research and the Department of Medicine, Wellington School of Medicine, Wellington South, New Zealand; ‡Institut für Virologie und Immunbiologie der Universität Würzburg, D-97070 Würzburg, Germany; and §Swiss Institute of Technology, Institute of Toxicology, CH-8603 Schwerzenbach, Switzerland
Bernhard Ryffel
From *The Malaghan Institute of Medical Research and the Department of Medicine, Wellington School of Medicine, Wellington South, New Zealand; ‡Institut für Virologie und Immunbiologie der Universität Würzburg, D-97070 Würzburg, Germany; and §Swiss Institute of Technology, Institute of Toxicology, CH-8603 Schwerzenbach, Switzerland
Annelise Schimpl
From *The Malaghan Institute of Medical Research and the Department of Medicine, Wellington School of Medicine, Wellington South, New Zealand; ‡Institut für Virologie und Immunbiologie der Universität Würzburg, D-97070 Würzburg, Germany; and §Swiss Institute of Technology, Institute of Toxicology, CH-8603 Schwerzenbach, Switzerland
Karen Rivett
From *The Malaghan Institute of Medical Research and the Department of Medicine, Wellington School of Medicine, Wellington South, New Zealand; ‡Institut für Virologie und Immunbiologie der Universität Würzburg, D-97070 Würzburg, Germany; and §Swiss Institute of Technology, Institute of Toxicology, CH-8603 Schwerzenbach, Switzerland
Address correspondence to Klaus Erb, The Malaghan Institute of Medical Research, P.O. Box 7060, Wellington South, New Zealand.
The authors wish to thank Dr. G. LeGros, Dr. F. Ronchese, and Dr. Paige Lacy (Malaghan Institute of Medical Research, Wellington, New Zealand) for providing reagents and their critical discussions.
This work was supported by the Deutsche Forschungsgemeinschaft (SFB 165), the Bundesministerium für Forschung und Technologie (AIDS-Scholarship), Germany, and Fonds der Chemischen Industrie.
1 Abbreviations used in this paper: AIHA, autoantibody-induced hemolytic anemia; ANA, anti-nuclear antigen; ASMA, anti-smooth muscle antigen; ENA, endonuclear antigen; MMTV, murine mammary tumor viruses; SLE, systemic lupus erythematosus; tg, transgenic.
Received:
July 16 1996
Revision Received:
September 27 1996
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1997
J Exp Med (1997) 185 (2): 329–340.
Article history
Received:
July 16 1996
Revision Received:
September 27 1996
Citation
Klaus J. Erb, Beate Rüger, Maja von Brevern, Bernhard Ryffel, Annelise Schimpl, Karen Rivett; Constitutive Expression of Interleukin (IL)-4 In Vivo Causes Autoimmune-type Disorders in Mice. J Exp Med 20 January 1997; 185 (2): 329–340. doi: https://doi.org/10.1084/jem.185.2.329
Download citation file:
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Sign in via your Institution
Sign in via your InstitutionEmail alerts
Advertisement
