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 antibodymediated 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 × 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-antigp70 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 lupuslike 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.
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6 January 1997
Article|
January 01 1997
Interleukin-4 Protects against a Genetically Linked Lupus-like Autoimmune Syndrome
Marie-Laure Santiago,
Marie-Laure Santiago
From the *Institut National de la Santé et de la Recherche Médicale U 291, F-34197 Montpellier, France; ‡Department of Pathology, Medical Center of the University of Geneva, CH-1211 Geneva 4, Switzerland; and §Institute for Genetics, University of Cologne, D-50931 Cologne, Germany
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Liliane Fossati,
Liliane Fossati
From the *Institut National de la Santé et de la Recherche Médicale U 291, F-34197 Montpellier, France; ‡Department of Pathology, Medical Center of the University of Geneva, CH-1211 Geneva 4, Switzerland; and §Institute for Genetics, University of Cologne, D-50931 Cologne, Germany
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Chantal Jacquet,
Chantal Jacquet
From the *Institut National de la Santé et de la Recherche Médicale U 291, F-34197 Montpellier, France; ‡Department of Pathology, Medical Center of the University of Geneva, CH-1211 Geneva 4, Switzerland; and §Institute for Genetics, University of Cologne, D-50931 Cologne, Germany
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Werner Müller,
Werner Müller
From the *Institut National de la Santé et de la Recherche Médicale U 291, F-34197 Montpellier, France; ‡Department of Pathology, Medical Center of the University of Geneva, CH-1211 Geneva 4, Switzerland; and §Institute for Genetics, University of Cologne, D-50931 Cologne, Germany
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Shozo Izui,
Shozo Izui
From the *Institut National de la Santé et de la Recherche Médicale U 291, F-34197 Montpellier, France; ‡Department of Pathology, Medical Center of the University of Geneva, CH-1211 Geneva 4, Switzerland; and §Institute for Genetics, University of Cologne, D-50931 Cologne, Germany
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Luc Reininger
Luc Reininger
From the *Institut National de la Santé et de la Recherche Médicale U 291, F-34197 Montpellier, France; ‡Department of Pathology, Medical Center of the University of Geneva, CH-1211 Geneva 4, Switzerland; and §Institute for Genetics, University of Cologne, D-50931 Cologne, Germany
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Marie-Laure Santiago
From the *Institut National de la Santé et de la Recherche Médicale U 291, F-34197 Montpellier, France; ‡Department of Pathology, Medical Center of the University of Geneva, CH-1211 Geneva 4, Switzerland; and §Institute for Genetics, University of Cologne, D-50931 Cologne, Germany
Liliane Fossati
From the *Institut National de la Santé et de la Recherche Médicale U 291, F-34197 Montpellier, France; ‡Department of Pathology, Medical Center of the University of Geneva, CH-1211 Geneva 4, Switzerland; and §Institute for Genetics, University of Cologne, D-50931 Cologne, Germany
Chantal Jacquet
From the *Institut National de la Santé et de la Recherche Médicale U 291, F-34197 Montpellier, France; ‡Department of Pathology, Medical Center of the University of Geneva, CH-1211 Geneva 4, Switzerland; and §Institute for Genetics, University of Cologne, D-50931 Cologne, Germany
Werner Müller
From the *Institut National de la Santé et de la Recherche Médicale U 291, F-34197 Montpellier, France; ‡Department of Pathology, Medical Center of the University of Geneva, CH-1211 Geneva 4, Switzerland; and §Institute for Genetics, University of Cologne, D-50931 Cologne, Germany
Shozo Izui
From the *Institut National de la Santé et de la Recherche Médicale U 291, F-34197 Montpellier, France; ‡Department of Pathology, Medical Center of the University of Geneva, CH-1211 Geneva 4, Switzerland; and §Institute for Genetics, University of Cologne, D-50931 Cologne, Germany
Luc Reininger
From the *Institut National de la Santé et de la Recherche Médicale U 291, F-34197 Montpellier, France; ‡Department of Pathology, Medical Center of the University of Geneva, CH-1211 Geneva 4, Switzerland; and §Institute for Genetics, University of Cologne, D-50931 Cologne, Germany
Address correspondence to Dr. L. Reininger, Laboratoire d'Immuno-Rhumatologie, Faculté de Médicine, 27 Boulevard Jean Moulin, F-13005, Marseille, France.
This work was supported by grants from the Association de Recherche sur la Polyarthrite, The Swiss National Foundation for Scientific Research, and the Research on Intractable Diseases from the Ministry of Health and Welfare, Japan.
1Abbreviations used in this paper: gp70 IC, gp70-anti-gp70 immune complex; HGG, human IgG; NIP, 4-hydroxy-3-iodo-5-nitrophenyl acetyl.
Received:
October 02 1996
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1997
J Exp Med (1997) 185 (1): 65–70.
Article history
Received:
October 02 1996
Citation
Marie-Laure Santiago, Liliane Fossati, Chantal Jacquet, Werner Müller, Shozo Izui, Luc Reininger; Interleukin-4 Protects against a Genetically Linked Lupus-like Autoimmune Syndrome. J Exp Med 6 January 1997; 185 (1): 65–70. doi: https://doi.org/10.1084/jem.185.1.65
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