Mannosylated self-peptide inhibits the development of experimental autoimmune encephalomyelitis via expansion of nonencephalitogenic T cells.
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.
Kel
Junda M
JM
Business Unit Biosciences, TNO Quality of Life, Leiden, The Netherlands. j.m.kel@amc.uva.nl
Slütter
Bram
B
Drijfhout
Jan Wouter
JW
Koning
Frits
F
Nagelkerken
Lex
L
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
D000939:Epitopes; D010455:Peptides; D037342:Pertussis Toxin; D008358:Mannose