Synthetic Peptide Dendrimers Block the Development and Expression of Experimental Allergic Encephalomyelitis

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 PLP139–151-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.