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Soluble mannosylated myelin peptide inhibits the encephalitogenicity of autoreactive T cells during experimental autoimmune encephalomyelitis

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Author: Kel, J. · Oldenampsen, J. · Luca, M. · Drijfhout, J.W. · Koning, F. · Nagelkerken, L.
Type:article
Date:2007
Institution: TNO Kwaliteit van Leven
Source:American Journal of Pathology, 1, 170, 272-280
Identifier: 239795
doi: doi:10.2353/ajpath.2007.060335
Keywords: Biology · Biomedical Research · gamma interferon · interleukin 23 · major histocompatibility antigen class 2 · myelin · proteolipid · autoantigen · epitope · lymphocyte antigen receptor · mannose · peptide fragment · proteolipid protein · proteolipid protein 139 151 · proteolipid protein 139-151 · allergic encephalomyelitis · animal cell · animal experiment · animal model · animal tissue · article · controlled study · drug mechanism · female · histopathology · immunization · immunomodulation · immunoreactivity · incidence · macrophage · mouse · nonhuman · priority journal · solubility · spinal cord · T lymphocyte · animal · chemistry · drug effect · immunology · inflammation · lymphocyte activation · pathology · Animals · Autoantigens · Encephalomyelitis, Autoimmune, Experimental · Female · Immunodominant Epitopes · Inflammation · Lymphocyte Activation · Mannose · Mice · Myelin Proteolipid Protein · Peptide Fragments · Receptors, Antigen, T-Cell · Spinal Cord · T-Lymphocytes

Abstract

We have previously shown that immunization with a mannosylated myelin peptide in complete adjuvant induces tolerance instead of disease in experimental autoimmune encephalomyelitis (EAE), a rodent model for multiple sclerosis. In this report we demonstrate that treatment with a soluble mannosylated epitope of proteolipid protein (M-PLP139-151) significantly inhibits disease mediated by autoreactive myelin-specific T cells during EAE. Treatment with M-PLP139-151, applied in different EAE models, significantly reduced the incidence of disease and the severity of clinical symptoms. Delayed-type hypersensitivity responses were abolished after peptide treatment, emphasizing the impact on peripheral T-cell reactivity. Histological analysis of spinal cord tissue from mice treated with M-PLP 139-151 revealed the presence of only few macrophages and T cells. Moreover, little expression of interferon-γ, interleukin-23, or major histocompatibility complex class II antigen was detected. Immune modulation by M-PLP139-151 was primarily antigen-specific because an irrelevant mannosylated peptide showed no significant effect on delayed-type hypersensitivity responses or on the course of EAE. Therefore, mannosylated antigens may represent a novel therapeutic approach for antigen-specific modulation of autoreactive T cells in vivo. Copyright © American Society for Investigative Pathology.