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Albert Einstein College of Medicine, Bronx, New York 10461, and the MRC Demyelinating Diseases Unit, Newcastle-on-Tyne, England
Abstract
The rabbit eye model has been used to investigate the role of antibody to CNS antigens in effecting primary demyelination. Serum from rabbits immunized with homologous spinal cord in complete Freund's adjuvant was injected into the vitreous of normal rabbits, alone, or admixed with the supernatants of activated lymphocytes which induce a mononuclear cell infiltrate. Neither immune serum alone nor the nonspecific inflammatory response induced by the lymphocyte supernatants was capable of causing primary demyelination. In contrast, injection of products of activated lymphocytes plus anti-CNS antibodies induced focal primary demyelination. The demyelinating activity was found in the serum of animals that had been specifically immunized to CNS antigens and was not found in the serum of normal rabbits or serum from rabbits immunized with homologous lung or kidney in FCA or FCA alone. By ammonium sulfate precipitation the factor was shown to be present in the globulin fraction of the serum. It was removed by an immunoadsorbent column of sheep anti-rabbit IgG, and the adsorbed IgG, upon elution, retained the activity. It was relatively stable to heating at 56°C for 30 min. Light microscopic examination indicated that the primary demyelination occurred in the vicinity of the invading cells, and electron microscopy suggested an active stripping of myelin by these cells. These results establish an antibody-dependent cell-mediated mechanism for primary demyelination.
Footnotes
1 This work was supported by Multiple Sclerosis Society Grant RG 1006-A-1, and National Institutes of Health Grants NS 11920-02 and AI 07118.
2 Albert Einstein College of Medicine, Bronx, New York 10461.
3 MRC Demyelinating Diseases Unit, Newcastle-on-Tyne, England. Present address: New York State Institute for Basic Research in Mental Retardation, Staten Island, New York 10314.
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