Soluble mannosylated myelin peptide inhibits the encephalitogenicity of autoreactive T cells during experimental autoimmune encephalomyelitis.
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-PLP(139-151)) significantly inhibits disease mediated by autoreactive myelin-specific T cells during EAE. Treatment with M-PLP(139-151), 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-gamma, interleukin-23, or major histocompatibility complex class II antigen was detected. Immune modulation by M-PLP(139-151) 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.
Kel
Junda
J
Business Unit Biomedical Research, TNO Quality of Life, Leiden, The Netherlands.
Oldenampsen
Judith
J
Luca
Mariken
M
Drijfhout
Jan Wouter
JW
Koning
Frits
F
Nagelkerken
Lex
L
D000818:Animals; D001324:Autoantigens / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D005260:Female; D016056:Immunodominant Epitopes / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D007249:Inflammation; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008358:Mannose; D051379:Mice; D018991:Myelin Proteolipid Protein / Q000737:chemistry / Q000494:pharmacology*; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D001324:Autoantigens; D016056:Immunodominant Epitopes; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; C435023:myelin proteolipid protein (139-151); D008358:Mannose