The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1999/3/1005/ $5.00
The Journal of Experimental Medicine, Volume 189, Number 6, March 15, 1999 1005-1010

Brief Definitive Reports

Transgenic Interleukin 10 Prevents Induction of Experimental Autoimmune Encephalomyelitis

Daniel J. Cua*, Herve Groux{ddagger}, David R. Hinton||,¶, Stephen A. Stohlman§,¶, and Robert L. Coffman*

From the * DNAX Research Institute of Molecular and Cellular Biology, Inc., Palo Alto, California 94304; {ddagger} 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

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.

Key Words: major histocompatibility complex class II promoter–regulated interleukin 10 • myelin-reactive T cells • immune regulation • autoimmunity

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.


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