The effectiveness of interleukin 10 (IL-10) in the treatment of autoimmune-mediated central nervous system inflammation is controversial. Studies of the model system, experimental autoimmune encephalomyelitis (EAE), using various routes, regimens, and delivery methods of IL-10 suggest that these variables may affect its immunoregulatory function. To study the influence of these factors on IL-10 regulation of EAE pathogenesis, we have analyzed transgenic mice expressing human IL-10 (hIL-10) transgene under the control of a class II major histocompatibility complex (MHC) promoter. The hIL-10 transgenic mice are highly resistant to EAE induced by active immunization, and this resistance appears to be mediated by suppression of autoreactive T cell function. Myelin-reactive T helper 1 cells are induced but nonpathogenic in the IL-10 transgenic mice. Antibody depletion confirmed that EAE resistance is dependent on the presence of the transgenic IL-10. Mice expressing the hIL-10 transgene but not the endogenous murine IL-10 gene demonstrated that transgenic IL-10 from MHC class II–expressing cells is sufficient to block induction of EAE. This study demonstrates that IL-10 can prevent EAE completely if present at appropriate levels and times during disease induction.
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15 March 1999
Brief Definitive Report|
March 15 1999
Transgenic Interleukin 10 Prevents Induction of Experimental Autoimmune Encephalomyelitis
Daniel J. Cua,
Daniel J. Cua
From the *DNAX Research Institute of Molecular and Cellular Biology, Inc., Palo Alto, California 94304; ‡Institut National de la Santé et de la Recherche Médicale, U343 Hopital de I'Archet, 06200 Nice, France; and the Department of §Molecular Microbiology and Immunology, the ‖ Department of Pathology, and the ¶Department of Neurology, University of Southern California at Los Angeles School of Medicine, Los Angeles, California 90033
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Herve Groux,
Herve Groux
From the *DNAX Research Institute of Molecular and Cellular Biology, Inc., Palo Alto, California 94304; ‡Institut National de la Santé et de la Recherche Médicale, U343 Hopital de I'Archet, 06200 Nice, France; and the Department of §Molecular Microbiology and Immunology, the ‖ Department of Pathology, and the ¶Department of Neurology, University of Southern California at Los Angeles School of Medicine, Los Angeles, California 90033
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David R. Hinton,
David R. Hinton
From the *DNAX Research Institute of Molecular and Cellular Biology, Inc., Palo Alto, California 94304; ‡Institut National de la Santé et de la Recherche Médicale, U343 Hopital de I'Archet, 06200 Nice, France; and the Department of §Molecular Microbiology and Immunology, the ‖ Department of Pathology, and the ¶Department of Neurology, University of Southern California at Los Angeles School of Medicine, Los Angeles, California 90033
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Stephen A. Stohlman,
Stephen A. Stohlman
From the *DNAX Research Institute of Molecular and Cellular Biology, Inc., Palo Alto, California 94304; ‡Institut National de la Santé et de la Recherche Médicale, U343 Hopital de I'Archet, 06200 Nice, France; and the Department of §Molecular Microbiology and Immunology, the ‖ Department of Pathology, and the ¶Department of Neurology, University of Southern California at Los Angeles School of Medicine, Los Angeles, California 90033
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Robert L. Coffman
Robert L. Coffman
From the *DNAX Research Institute of Molecular and Cellular Biology, Inc., Palo Alto, California 94304; ‡Institut National de la Santé et de la Recherche Médicale, U343 Hopital de I'Archet, 06200 Nice, France; and the Department of §Molecular Microbiology and Immunology, the ‖ Department of Pathology, and the ¶Department of Neurology, University of Southern California at Los Angeles School of Medicine, Los Angeles, California 90033
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Daniel J. Cua
From the *DNAX Research Institute of Molecular and Cellular Biology, Inc., Palo Alto, California 94304; ‡Institut National de la Santé et de la Recherche Médicale, U343 Hopital de I'Archet, 06200 Nice, France; and the Department of §Molecular Microbiology and Immunology, the ‖ Department of Pathology, and the ¶Department of Neurology, University of Southern California at Los Angeles School of Medicine, Los Angeles, California 90033
Herve Groux
From the *DNAX Research Institute of Molecular and Cellular Biology, Inc., Palo Alto, California 94304; ‡Institut National de la Santé et de la Recherche Médicale, U343 Hopital de I'Archet, 06200 Nice, France; and the Department of §Molecular Microbiology and Immunology, the ‖ Department of Pathology, and the ¶Department of Neurology, University of Southern California at Los Angeles School of Medicine, Los Angeles, California 90033
David R. Hinton
From the *DNAX Research Institute of Molecular and Cellular Biology, Inc., Palo Alto, California 94304; ‡Institut National de la Santé et de la Recherche Médicale, U343 Hopital de I'Archet, 06200 Nice, France; and the Department of §Molecular Microbiology and Immunology, the ‖ Department of Pathology, and the ¶Department of Neurology, University of Southern California at Los Angeles School of Medicine, Los Angeles, California 90033
Stephen A. Stohlman
From the *DNAX Research Institute of Molecular and Cellular Biology, Inc., Palo Alto, California 94304; ‡Institut National de la Santé et de la Recherche Médicale, U343 Hopital de I'Archet, 06200 Nice, France; and the Department of §Molecular Microbiology and Immunology, the ‖ Department of Pathology, and the ¶Department of Neurology, University of Southern California at Los Angeles School of Medicine, Los Angeles, California 90033
Robert L. Coffman
From the *DNAX Research Institute of Molecular and Cellular Biology, Inc., Palo Alto, California 94304; ‡Institut National de la Santé et de la Recherche Médicale, U343 Hopital de I'Archet, 06200 Nice, France; and the Department of §Molecular Microbiology and Immunology, the ‖ Department of Pathology, and the ¶Department of Neurology, University of Southern California at Los Angeles School of Medicine, Los Angeles, California 90033
Address correspondence to Robert L. Coffman, DNAX Institute of Molecular and Cellular Biology, Inc., 901 California Ave., Palo Alto, CA 94304. Phone: 650-496-1261; Fax: 650-496-1200; E-mail: coffman @dnax.org
DNAX is supported by the Schering Plough Corporation.
Received:
November 12 1998
Revision Received:
January 11 1999
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1999
J Exp Med (1999) 189 (6): 1005–1010.
Article history
Received:
November 12 1998
Revision Received:
January 11 1999
Citation
Daniel J. Cua, Herve Groux, David R. Hinton, Stephen A. Stohlman, Robert L. Coffman; Transgenic Interleukin 10 Prevents Induction of Experimental Autoimmune Encephalomyelitis . J Exp Med 15 March 1999; 189 (6): 1005–1010. doi: https://doi.org/10.1084/jem.189.6.1005
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