Title
Soluble mannosylated myelin peptide inhibits the encephalitogenicity of autoreactive T cells during experimental autoimmune encephalomyelitis
Author
Kel, J.
Oldenampsen, J.
Luca, M.
Drijfhout, J.W.
Koning, F.
Nagelkerken, L.
TNO Kwaliteit van Leven
Publication year
2007
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.
Subject
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
To reference this document use:
http://resolver.tudelft.nl/uuid:ed5697c7-65fd-4572-ab0a-6683eca7293d
DOI
https://doi.org/10.2353/ajpath.2007.060335
TNO identifier
239795
ISSN
0002-9440
Source
American Journal of Pathology, 170 (1), 272-280
Document type
article