TY - JOUR
T1 - Antigen presenting capacity of brain microvasculature in altered peptide ligand modulation of experimental allergic encephalomyelitis
AU - Santambrogio, L.
AU - Pakaski, M.
AU - Wong, M. L.
AU - Cipriani, B.
AU - Brosnan, C. F.
AU - Lees, M. B.
AU - Dorf, M. E.
N1 - Funding Information:
The authors thank Dr. Raymond Sobel for extensive discussions throughout this project. This work was supported with grants from the National Multiple Sclerosis Society (PP0480T), the Multiple Sclerosis Foundation, the National Institutes of Health (NS16945, NS31152, and HD04147), and a fellowship from the Italian Multiple Sclerosis Society.
PY - 1999/1/1
Y1 - 1999/1/1
N2 - Co-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., Franco, A., Sette, A., Sobel, R.A., Lees, M.B., 1994. A single TCR antagonist peptide inhibits experimental allergic encephalomyelitis mediated by a diverse 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. Neuroimmunol. 81, 1-13]. Clinical protection was noted despite extensive central nervous system inflammation observed after co-immunization with native and altered peptides. To extend our previous reports on this model, we now compare MHC class II expression and antigen presenting cell activity of cells associated with the blood-brain barrier in diseased and protected mice. Immunohistochemical studies identified MHC class II products on both the endothelial and microglial/macrophage populations. Ex vivo experiments suggested a correlation between the reduced clinical disease observed in the co-immunized mice and the antigen presenting activity of cells at the blood- brain barrier. The results suggest that antigen presenting activity is primarily mediated by macrophage-lineage cells of the central nervous system.
AB - Co-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., Franco, A., Sette, A., Sobel, R.A., Lees, M.B., 1994. A single TCR antagonist peptide inhibits experimental allergic encephalomyelitis mediated by a diverse 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. Neuroimmunol. 81, 1-13]. Clinical protection was noted despite extensive central nervous system inflammation observed after co-immunization with native and altered peptides. To extend our previous reports on this model, we now compare MHC class II expression and antigen presenting cell activity of cells associated with the blood-brain barrier in diseased and protected mice. Immunohistochemical studies identified MHC class II products on both the endothelial and microglial/macrophage populations. Ex vivo experiments suggested a correlation between the reduced clinical disease observed in the co-immunized mice and the antigen presenting activity of cells at the blood- brain barrier. The results suggest that antigen presenting activity is primarily mediated by macrophage-lineage cells of the central nervous system.
KW - Brain endothelial cells
KW - Experimental allergic encephalomyelitis
KW - Inflammation
KW - Perivascular macrophages
KW - Proteolipid protein
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U2 - 10.1016/S0165-5728(98)00203-3
DO - 10.1016/S0165-5728(98)00203-3
M3 - Article
C2 - 10378871
AN - SCOPUS:0032943376
SN - 0165-5728
VL - 93
SP - 81
EP - 91
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
IS - 1-2
ER -