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Studies on Demyelination by Activated Lymphocytes in the Rabbit Eye

I. Effects of a Mononuclear Cell Infiltrate Induced by Products of Activated Lymphocytes¹

Albert Einstein College of Medicine, Bronx, New York 10461, and the MRC Demyelinating Diseases Unit, Newcastle-on-Tyne, England

Abstract

The role of products of activated lymphocytes (PAL) in the pathogenesis of primary demyelination has been investigated in the rabbit eye model. Supernatant factors were prepared from rabbit lymph node cells specifically activated in vitro with non-brain antigen (PPD) or nonspecifically activated by mitogen (concanavalin A-Sepharose). The supernatants were shown to contain migration-inhibitory factor (MIF) activity and skin-reactive factor (SRF) activity, mediators of delayed-type hypersensitivity. The active supernatants were injected into the vitreous of the right eye to determine their ability to promote demyelination of the retinal fibers. The left eye received a supernatant prepared from unstimulated cells. In normal rabbits and in rabbits sensitized with lung or kidney, or FCA alone, or infected with living BCG, the lymphocyte products failed to damage myelin directly. Nor was the mononuclear cell infiltrate induced by the PAL specifically destructive to myelin. However, in rabbits sensitized to homologous spinal cord, the lymphocyte products induced a demyelinating lesion within the retinal fibers. This result indicates a role for PAL, in concert with other as yet undefined functions, in the initiation of an autoimmune demyelinating lesion in the CNS. The use of PAL to induce a mononuclear cell infiltration of the rabbit eye extends the usefulness of the rabbit eye model for studies of the pathogenesis of 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.