Article

Limited sufficiency of antigen presentation by dendritic cells in models of central nervous system autoimmunity.

Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA 19004, USA.
Journal of Autoimmunity (Impact Factor: 7.02). 02/2011; 36(1):56-64. DOI: 10.1016/j.jaut.2010.10.006
Source: PubMed

ABSTRACT 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.

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Available from: Robert J Mikesell, Jul 12, 2015
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    • "For the combined analysis of three different experiments (n ¼ 7e8 mice/experiment), the clinical scores were normalized to the maximum disease score observed in each experiment and represented as % maximal disease score. Ex vivo quantification of antigen-specific, IFN-g and IL-17-producing CD4 þ T cells was performed as described previously [22]. Briefly, draining lymph nodes were isolated from mice and re-stimulated with MOG peptide or media alone for 18 h. "
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    • "The infiltration of DCs from the periphery during neuroinflammatory autoimmunity has been studied particularly in EAE models of MS. Studies indicate that DCs are capable of perpetuating CNS-targeted autoimmunity when antigens are readily available, but other APCs (B cells, microglia) may be required to efficiently initiate pathogenic CD4 T cell responses (Wu et al. 2011). In studies using transgenic mice in which APC capacity is restricted only to peripheral blood DCs, peripheral DCs seem to be sufficient to reactivate myelin-specific T cells in order to initiate EAE (Greter et al. 2005). "
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