The Journal of Experimental Medicine
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Published 15 July 2002. doi:10.1084/jem.20011061
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© Rockefeller University Press, 0022-1007/2002/7/217/ $5.00
The Journal of Experimental Medicine, Volume 196, Number 2, July 15, 2002 217-227
On the Role of Dendritic Cells in Peripheral T Cell Tolerance and Modulation of Autoimmunity

Kevin L. Legge1, Randal K. Gregg1, Roberto Maldonado-Lopez2, Lequn Li1, Jacque C. Caprio1, Muriel Moser2 and Habib Zaghouani1

1 Department of Microbiology, University of Tennessee, Knoxville, TN 37996
2 Institut de Biologie et Medecine Moléculaires, Université Libre de Bruxelles, 6041 Gosselies, Belgium

Address correspondence to Habib Zaghouani, The University of Missouri School of Medicine, Dept. of Molecular Microbiology & Immunology, M616 Medical Sciences Building, Columbia, MO 65212. Phone: 573-884-0659; Fax: 573-882-4287; E-mail: zaghouanih{at}health.missouri.edu

Recently, it has become clear that dendritic cells (DCs) are essential for the priming of T cell responses. However, their role in the maintenance of peripheral T cell tolerance remains largely undefined. Herein, an antigen-presenting cell (APC) transfer system was devised and applied to experimental allergic encephalomyelitis (EAE), to evaluate the contribution that DCs play in peripheral T cell tolerance. The CD8{alpha}-CD4+ subset, a minor population among splenic DCs, was found to mediate both tolerance and bystander suppression against diverse T cell specificities. Aggregated (agg) Ig-myelin oligodendrocyte glycoprotein (MOG), an Ig chimera carrying the MOG 35–55 peptide, binds and cross-links Fc{gamma}R on APC leading to efficient peptide presentation and interleukin (IL)-10 production. Furthermore, administration of agg Ig-MOG into diseased mice induces relief from clinical EAE involving multiple epitopes. Such recovery could not occur in Fc{gamma}R-deficient mice where both uptake of Ig-MOG and IL-10 production are compromised. However, reconstitution of these mice with DC populations incorporating the CD8{alpha}-CD4+ subset restored Ig-MOG–mediated reversal of EAE. Transfer of CD8{alpha}+ or even CD8{alpha}-CD4- DCs had no effect on the disease. These findings strongly implicate DCs in peripheral tolerance and emphasize their functional potency, as a small population of DCs was able to support effective suppression of autoimmunity.

Key Words: autoimmunity • antigen delivery • dendritic cells • peripheral T cell tolerance • Fc{gamma} receptors


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