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-gamma-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-gamma-producing cells in the CNS of PLP(139-151) MAP-treated animals.
Wegmann
Keith W
KW
Veterans Affairs Medical Center, Oregon Health & Science University, Portland, OR 97239, USA.
Wagner
Cynthia R
CR
Whitham
Ruth H
RH
Hinrichs
David J
DJ
D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002490:Central Nervous System / Q000473:pathology; D050091:Dendrimers / Q000627:therapeutic use*; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000517:prevention & control*; D005260:Female; D051379:Mice; D010455:Peptides / Q000627:therapeutic use*; D011510:Proteolipids; D055502:Secondary Prevention; D013601:T-Lymphocytes
D050091:Dendrimers; D010455:Peptides; D011510:Proteolipids