J Exp Med 2002 Jul 15;196(2):217-27
Legge KL, Gregg RK, Maldonado-Lopez R, Li L, Caprio JC, Moser M, Zaghouani H.
Department of Microbiology, University of Tennessee, Knoxville, TN 37996. Institut de Biologie et Medecine Moleculaires, Universite Libre de Bruxelles, 6041 Gosselies, Belgium.
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 CD8alpha(-)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 FcgammaR 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 FcgammaR-deficient mice where both uptake of Ig-MOG and IL-10 production are compromised.
However, reconstitution of these mice with DC populations incorporating the CD8alpha(-)CD4(+) subset restored Ig-MOG-mediated reversal of EAE.
Transfer of CD8alpha(+) or even CD8alpha(-)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.