Journal article
On the Role of Dendritic Cells in Peripheral T Cell Tolerance and Modulation of Autoimmunity
The Journal of experimental medicine, Vol.196(2), pp.217-227
07/15/2002
DOI: 10.1084/jem.20011061
PMCID: PMC2193920
PMID: 12119346
Abstract
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 CD8α−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 FcγR 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 FcγR-deficient mice where both uptake of Ig-MOG and IL-10 production are compromised. However, reconstitution of these mice with DC populations incorporating the CD8α−CD4+ subset restored Ig-MOG–mediated reversal of EAE. Transfer of CD8α+ or even CD8α−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.
Details
- Title: Subtitle
- On the Role of Dendritic Cells in Peripheral T Cell Tolerance and Modulation of Autoimmunity
- Creators
- Kevin L Legge - Department of Microbiology, University of Tennessee, Knoxville, TN 37996Randal K Gregg - Department of Microbiology, University of Tennessee, Knoxville, TN 37996Roberto Maldonado-Lopez - Institut de Biologie et Medecine Moléculaires, Université Libre de Bruxelles, 6041 Gosselies, BelgiumLequn Li - Department of Microbiology, University of Tennessee, Knoxville, TN 37996Jacque C Caprio - Department of Microbiology, University of Tennessee, Knoxville, TN 37996Muriel Moser - Institut de Biologie et Medecine Moléculaires, Université Libre de Bruxelles, 6041 Gosselies, BelgiumHabib Zaghouani - Department of Microbiology, University of Tennessee, Knoxville, TN 37996
- Resource Type
- Journal article
- Publication Details
- The Journal of experimental medicine, Vol.196(2), pp.217-227
- DOI
- 10.1084/jem.20011061
- PMID
- 12119346
- PMCID
- PMC2193920
- ISSN
- 0022-1007
- eISSN
- 1540-9538
- Language
- English
- Date published
- 07/15/2002
- Academic Unit
- Microbiology and Immunology; Pathology
- Record Identifier
- 9984047985102771
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