Antigen presenting capacity of brain microvasculature in altered peptide ligand modulation of experimental allergic encephalomyelitis

Go-immunization with an altered peptide ligand (LR) partially protects SJL mice from proteolipid protein peptide 139-151-induced experimental allergic encephalomyelitis [Kuchroo, V.K., Greer, J.M., Kaul, D., Ishioka, G.Y., Fr ance, A., Sette, A., Sobel, R.A., Lees, M.B., 1994. A single TCR antagonist peptide inhibits experimental allergic encephalomyelitis mediated by a div erse T cell repertoire. J. Immunol. 153, 3326-3336; Santambrogio, L., Lees, M.B., Sobel, R.A., 1998. Altered peptide ligand modulation of experimental allergic encephalomyelitis: immune responses within the CNS. J. Neuroimmun ol. 81, 1-13]. Clinical protection was noted despite extensive central nerv ous system inflammation observed after co-immunization with native and alte red peptides. To extend our previous reports on this model, we now compare MHC class II expression and antigen presenting cell activity of cells assoc iated with the blood-brain barrier in diseased and protected mice. Immunohi stochemical studies identified MHC class II products on both the endothelia l and microglial/macrophage populations. Ex vivo experiments suggested a co rrelation between the reduced clinical disease observed in the co-immunized mice and the antigen presenting activity of cells at the blood-brain barri er. The results suggest that antigen presenting activity is primarily media ted by macrophage-lineage cells of the central nervous system. (C) 1999 Els evier Science B.V. All rights reserved.