title: Mannosylated self-peptide inhibits the development of experimental autoimmune encephalomyelitis via expansion of nonencephalitogenic T cells.
abstract: Tolerance to experimental autoimmune encephalomyelitis (EAE) in SJL mice can be induced by immunization with a mannosylated form of the proteolipid protein (M-PLP139-151), despite the presence of CFA. The state of tolerance is characterized by poor delayed-type hypersensitivity responses and the absence of clinical EAE symptoms. In vivo monitoring of CFSE-labeled PLP139-151-specific TCR-transgenic (5B6) T cells revealed that immunization with M-PLP139-151 increases the clonal expansion of 5B6 T cells that do not develop full effector functions. Moreover, nonfunctional T cells obtained from M-PLP139-151-immunized mice showed poor blastogenesis and were unable to transfer EAE to naïve recipients. Nevertheless, the in vitro production of cytokines and chemokines associated with EAE was unaffected. Importantly, tolerance induced by M-PLP139-151 was abrogated by the administration of pertussis toxin, resulting in EAE development. Our results suggest that M-PLP139-151 inhibits EAE development by affecting the differentiation of T cells into encephalitogenic effector cells.
authors.affiliation: Business Unit Biosciences, TNO Quality of Life, Leiden, The Netherlands. j.m.kel@amc.uva.nl
authors.forename: Junda M
authors.initials: JM
authors.lastname: Kel
authors.forename: Bram
authors.initials: B
authors.lastname: Slütter
authors.forename: Jan Wouter
authors.initials: JW
authors.lastname: Drijfhout
authors.forename: Frits
authors.initials: F
authors.lastname: Koning
authors.forename: Lex
authors.initials: L
authors.lastname: Nagelkerken
mesh_terms: D000818:Animals; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D002999:Clone Cells; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000517:prevention & control*; D000939:Epitopes; D005260:Female; D007108:Immune Tolerance; D007114:Immunization; D008358:Mannose / Q000378:metabolism*; D051379:Mice; D010455:Peptides / Q000276:immunology*; D037342:Pertussis Toxin / Q000494:pharmacology; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects
chemical_list: D000939:Epitopes; D010455:Peptides; D037342:Pertussis Toxin; D008358:Mannose