Synergistic interaction between Toll-like receptor agonists is required for induction of experimental autoimmune encephalomyelitis in Lewis rats.

To investigate whether TLR agonists can replace mycobacteria in adjuvant to induce EAE in Lewis rats, we immunized rats with MBP peptide (MBP(68-86)) in IFA, supplemented with TLR agonists. Rats immunized with MBP(68-86) plus CpG-ODN or LPS in IFA did not develop EAE. In contrast, rats immunized with MBP(68-86) plus CpG-ODN and LPS in IFA developed clinical EAE. Spleen cells proliferated and secreted IFN-gamma in response to MBP(68-86), and secreted IL-6 and IL-12p40 in response to CpG-ODN and LPS. However, rats immunized with MBP(68-86) plus CpG-ODN and PolyI:C, a TLR3 agonist, did not develop EAE. We conclude that selected combinations of TLR agonists can facilitate the induction of EAE by MBP peptide via the innate immune system.