Aim: To explore the synergistic effect of MBP 68-86 and 87-99, on the inhibition of experimental autoimmune encephalomyelitis (EAE) in Lewis rat by nasal administration.
Methods: Three different MBP peptides(MBP 68-86, 87-99, and the non-encephalitogenic peptide 110-128) were synthesized and administrated nasally to Lewis rat on day-11, -10, -9, -8 and -7 prior to immunization with the guinea pig MBP (gp-MBP)+CFA, which was used to induce EAE. The protective effect on Lewis rat from EAE by the MBP peptides was evaluated.
Results: Protection was achieved with the encephalitogenic peptides MBP 68-86 and 87-99, MBP 68-86 being more potent, but not with MBP 110-128. Neither MBP 68-86 nor 87-99 used alone conferred complete protection to gp-MBP-induced EAE. In contrast, nasal administration of a mixture of MBP 68-86 and 87-99 completely blocked gp-MBP-induced EAE even at lower dosage than being used alone. Rats tolerized with MBP 68-86+87-99 nasally showed decreased T cell responses to MBP, reflected by lymphocyte proliferation and IFN-gamma ELISPOT assays. Rats tolerized with MBP 68-86+87-99 also had abrogated MBP-reactive IFN-gamma and TNF-alpha mRNA expression in lymph node cells compared to rats receiving MBP 110-128 nasally, while similar low levels of MBP-reactive TGF-beta and IL-4 mRNA expressing cells were observed in the two groups.
Conclusion: Nasal administration of encephalitogenic MBP peptides can induce antigen-specific T cell tolerance and confer incomplete protection to gp-MBP-induced EAE, and MBP 68-86 and 87-99 have synergistic effects. Non-regulatory mechanisms are proposed to be responsible for tolerance development after nasal peptide administration.