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(American Journal of Pathology. 2007;170:272-280.)
© 2007 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2007.060335

Soluble Mannosylated Myelin Peptide Inhibits the Encephalitogenicity of Autoreactive T Cells during Experimental Autoimmune Encephalomyelitis

Junda Kel*{dagger}, Judith Oldenampsen*, Mariken Luca*, Jan Wouter Drijfhout{dagger}, Frits Koning{dagger} and Lex Nagelkerken*

From the Business Unit Biomedical Research,* TNO Quality of Life, Leiden; and the Department of Immunohematology and Blood Transfusion,{dagger} Leiden University Medical Centre, Leiden, The Netherlands

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-PLP139-151 revealed the presence of only few macrophages and T cells. Moreover, little expression of interferon-{gamma}, 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.




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Copyright © 2007 by the American Society for Investigative Pathology.