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 PLP_139-151 MAPs were very efficient agents in preventing the development of clinical disease when administered after immunization with the PLP_139-151 monomeric encephalitogenic peptide in CFA. The treatment effect with these MAPs was peptide specific; irrelevant multimeric peptides such as guinea pig myelin basic protein GPBP_72-84 MAP (a dendrimeric octamer composed of the 72-84 peptide) and PLP_178-191 MAP (a dendrimeric octamer composed of the PLP_178-191 peptide) had no treatment effect on PLP _139-151-induced EAE. PLP_139-151 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. PLP_139-151 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 PLP_139-151 MAP-treated animals. The net effect of PLP_139-151 MAP treatment dramatically increases the ratio of Foxp3⁺ cells to Th17 and IFN-γ-producing cells in the CNS of PLP_139-151 MAP-treated animals.