Soluble mannosylated myelin peptide inhibits the encephalitogenicity of autoreactive T cells during experimental autoimmune encephalomyelitis
article
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.
Topics
Biomedical ResearchGamma interferonInterleukin 23Major histocompatibility antigen class 2MyelinProteolipidAutoantigenEpitopeLymphocyte antigen receptorMannosePeptide fragmentProteolipid proteinProteolipid protein 139 151Proteolipid protein 139-151Allergic encephalomyelitisAnimal cellAnimal experimentAnimal modelAnimal tissueControlled studyDrug mechanismFemaleHistopathologyImmunizationImmunomodulationImmunoreactivityIncidenceMacrophageMouseNonhumanPriority journalSolubilitySpinal cordT lymphocyteAnimalChemistryDrug effectImmunologyInflammationLymphocyte activationPathologyAnimalsAutoantigensEncephalomyelitis, Autoimmune, ExperimentalFemaleImmunodominant EpitopesInflammationLymphocyte ActivationMannoseMiceMyelin Proteolipid ProteinPeptide FragmentsReceptors, Antigen, T-CellSpinal CordT-Lymphocytes
TNO Identifier
239795
ISSN
00029440
Source
American Journal of Pathology, 170(1), pp. 272-280.
Pages
272-280
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