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 D1-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 allergic 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 the 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 restimulation with PLP139-151 and exhibited decreased frequencies of IL-2, IL-4, and IFN-gamma producing cells, but were still able to respond to third-party antigens. These combined results suggest the potential therapeutic value of 802-2 for inhibition of CD4(+) T cell neuroimmunological responses.
Edling
A E
AE
Department of Microbiology and Immunology, Jefferson Medical College, 233 S. 10th Street, Philadelphia, PA 19107, USA.
Choksi
S
S
Huang
Z
Z
Korngold
R
R
D000818:Animals; D015704:CD4 Antigens / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D010446:Peptide Fragments / Q000494:pharmacology* / Q000627:therapeutic use; D010456:Peptides, Cyclic / Q000494:pharmacology*; D013997:Time Factors
D015704:CD4 Antigens; D016207:Cytokines; D010446:Peptide Fragments; D010456:Peptides, Cyclic