Our overall research program is directed to an understanding of the role of proteolipid protein in the development, maintenance and function of CNS myelin. The proteolipid protein is quantitatively the major protein of CNS myelin and consequently its contribution should be considered in autoimmune phenomena involving the nervous system. Our fundamental hypothesis is that, in demyelinating diseases, the immune response involves multiple myelin components and that one of these components is the proteolipid protein. Although myelin basic protein is the principal antigen in the production of acute EAE, other antigens may participate, either directly or indirectly, both in the acute and chronic forms of the disease and in multiple sclerosis. To explore our hypothesis, the specific aims during the next grant period are: A. to study changes in immune cell populations during the development of disease produced by challenge with proteolipid apoprotein. Monoclonal antibodies to T-cells, IgM-bearing B-cells, and Ia antigens will be used to compare (a) peripheral blood lymphocyte populations, analyzed by flow cytometry, with (b) the number and distribution of these populations in brain and spinal cord sections. The analysis will give quantitative data in two species (rabbits and guinea pigs) for comparison of the dynamics of the immune response to proteolipid with that in other forms of EAE. B. to test whether apoprotein modulates immune challenge by other tissue components in experiments on apoprotein-sensitized animals subsequently challenged with other tissue components, and in adoptive transfer experiments. C. to analyze sera and CSF from patients with MS and other demyelinating disorders for proteolipid and anti-proteolipid antibodies. The major purpose or our experimental approach is to provide a broader view of overall events in different EAE models, as a means of contributing to the understanding of immunopathologic patterns in multiple sclerosis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS016945-05
Application #
3397250
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1981-01-01
Project End
1990-12-31
Budget Start
1985-01-01
Budget End
1985-12-31
Support Year
5
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Eunice Kennedy Shriver Center Mtl Retardatn
Department
Type
DUNS #
City
Waltham
State
MA
Country
United States
Zip Code
Santambrogio, L; Pakaski, M; Wong, M L et al. (1999) Antigen presenting capacity of brain microvasculature in altered peptide ligand modulation of experimental allergic encephalomyelitis. J Neuroimmunol 93:81-91
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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
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Lees, M B; Smith, F I; Dyer, C A et al. (1995) Expression of myelin proteolipid protein in oligodendrocytes and transfected cells. Prog Brain Res 105:295-303

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