Document Detail


Limited sufficiency of antigen presentation by dendritic cells in models of central nervous system autoimmunity.
MedLine Citation:
PMID:  21095100     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Experimental autoimmune encephalomyelitis (EAE), a model for the human disease multiple sclerosis (MS), is dependent upon the activation and effector functions of autoreactive CD4 T cells. Multiple interactions between CD4 T cells and major histocompatibility class II (MHCII)+ antigen presenting cells (APCs) must occur in both the periphery and central nervous system (CNS) to elicit autoimmunity. The identity of the MHCII+ APCs involved throughout this process remains in question. We investigated which APC in the periphery and CNS mediates disease using transgenic mice with MHCII expression restricted to dendritic cells (DCs). MHCII expression restricted to DCs results in normal susceptibility to peptide-mediated EAE. Indeed, radiation-sensitive bone marrow-derived DCs were sufficient for all APC functions during peptide-induced disease. However, DCs alone were inefficient at promoting disease after immunization with the myelin protein myelin oligodendrocyte glycoprotein (MOG), even in the presence of MHCII-deficient B cells. Consistent with a defect in disease induction following protein immunization, antigen presentation by DCs alone was incapable of mediating spontaneous optic neuritis. These results indicate that DCs are capable of perpetuating CNS-targeted autoimmunity when antigens are readily available, but other APCs are required to efficiently initiate pathogenic cognate CD4 T cell responses.
Authors:
Gregory F Wu; Kenneth S Shindler; Eric J Allenspach; Tom L Stephen; Hannah L Thomas; Robert J Mikesell; Anne H Cross; Terri M Laufer
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-11-20
Journal Detail:
Title:  Journal of autoimmunity     Volume:  36     ISSN:  1095-9157     ISO Abbreviation:  J. Autoimmun.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-31     Completed Date:  2011-04-28     Revised Date:  2012-02-02    
Medline Journal Info:
Nlm Unique ID:  8812164     Medline TA:  J Autoimmun     Country:  England    
Other Details:
Languages:  eng     Pagination:  56-64     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Ltd. All rights reserved.
Affiliation:
Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA 19004, USA. wug@neuro.wustl.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigen Presentation / immunology*
CD4-Positive T-Lymphocytes / immunology
Cell Separation
Dendritic Cells / immunology*
Encephalomyelitis, Autoimmune, Experimental / immunology*,  pathology
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Histocompatibility Antigens Class II / immunology
Lymphocyte Activation / immunology
Mice
Mice, Inbred C57BL
Mice, Transgenic
Optic Nerve / pathology
Spinal Cord / pathology
Grant Support
ID/Acronym/Agency:
K08 NS062138-01A1/NS/NINDS NIH HHS; R01 AI068819-02/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Histocompatibility Antigens Class II

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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