Journal of Leukocyte Biology
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Originally published online as doi:10.1189/jlb.0507312 on April 18, 2008

Published online before print April 18, 2008
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(Journal of Leukocyte Biology. 2008;84:182-190.)
© 2008 by Society for Leukocyte Biology

Mannosylated self-peptide inhibits the development of experimental autoimmune encephalomyelitis via expansion of nonencephalitogenic T cells

Junda M. Kel*,{dagger},1, Bram Slütter*, Jan Wouter Drijfhout{dagger}, Frits Koning{dagger} and Lex Nagelkerken*

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

1Correspondence at current address: Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands. E-mail: j.m.kel{at}amc.uva.nl

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.

Key Words: delayed-type hypersensitivity (DTH) • tolerance • C-type lectins







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