Effect of a cyclic heptapeptide based on the human CD4 domain 1 CC ' loop region on murine experimental allergic encephalomyelitis: inhibition of both primary and secondary responses

The 802-2 peptide, designed from the conserved DI-CC' loop region of human CD4, can disrupt CD4(+) T cell activation in both human and murine systems. Here. 802-2 was investigated for efficacy in acute murine experimental all ergic encephalomyelitis (EAE) models, and was found to significantly reduce the severity of disease when administered either before or after the onset of symptoms. 802-2 treatment during PLP139-151 induction of EAE rendered t he mice more resistant to subsequent rechallenge with antigen, and was also efficacious when initially administered during a secondary EAE response. T cells from 802-2-treated mice proliferated poorly to in vitro restimulatio n with PLP139-151 and exhibited decreased frequencies of IL-2, IL-4, and IF N-gamma producing cells, but were still able to respond to third-party anti gens. These combined results suggest the potential therapeutic value of 802 -2 for inhibition of CD4(+) T cell neuroimmunological responses. (C) 2001 E lsevier Science B.V. All rights reserved.