Synthetic peptide dendrimers block the development and expression of experimental allergic encephalomyelitis

Keith W. Wegmann, Cynthia R. Wagner, Ruth H. Whitham, David J. Hinrichs

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Multiple Ag peptides (MAPs) containing eight proteolipid protein (PLP) 139-151 peptides arranged around a dendrimeric branched lysine core were used to influence the expression and development of relapsing experimental allergic encephalomyelitis (EAE) in SJL mice. The PLP139-151 MAPs were very efficient agents in preventing the development of clinical disease when administered after immunization with the PLP139-151 monomeric encephalitogenic peptide in CFA. The treatment effect with these MAPs was peptide specific; irrelevant multimeric peptides such as guinea pig myelin basic protein GPBP72-84 MAP (a dendrimeric octamer composed of the 72-84 peptide) and PLP178-191 MAP (a dendrimeric octamer composed of the PLP178-191 peptide) had no treatment effect on PLP 139-151-induced EAE. PLP139-151 MAP treatment initiated after clinical signs of paralysis also altered the subsequent course of EAE; it limited developing signs of paralysis and effectively limited the severity and number of disease relapses in MAP-treated mice over a 60-day observation period. PLP139-151 MAP therapy initiated before disease onset acts to limit the numbers of Th17 and IFN-γ-producing cells that enter into the CNS. However, Foxp3+ cells entered the CNS in numbers equivalent for nontreated and PLP139-151 MAP-treated animals. The net effect of PLP139-151 MAP treatment dramatically increases the ratio of Foxp3+ cells to Th17 and IFN-γ-producing cells in the CNS of PLP139-151 MAP-treated animals.

Original languageEnglish (US)
Pages (from-to)3301-3309
Number of pages9
JournalJournal of Immunology
Volume181
Issue number5
DOIs
StatePublished - Sep 1 2008

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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