PATHOGENESIS OF VISNA .3. IMMUNE-RESPONSES TO CENTRAL NERVOUS-SYSTEM ANTIGENS IN EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS AND VISNA

  • 1 January 1976
    • journal article
    • research article
    • Vol. 35  (5) , 452-460
Abstract
Experimental allergic encephalomyelitis (EAE) was induced in sheep in pursuit of the hypothesis that an immune response against CNS antigens might play a role in the pathogenesis of visna. Nine to 12 days after sensitization with whole sheep brain and complete Freund''s adjuvant [Mycobacterium tuberculosis], approximately 50% of sheep developed a fulminating lethal form of EAE. Following a 2nd sensitization, another 20% of animals developed EAE whereas a residual 30% failed to develop any signs or histologic evidence of disease. A histologic comparison of EAE and visna indicated considerable similarity in the nature of the pathologic process. The distribution of lesions was quite different, suggesting cellular responses to 2 different antigens. Cell-mediated immunity to myelin basic protein, as measured by lymphocyte blast transformation, was minimally elevated in sheep sensitized with whole brain suspension in complete Freund''s adjuvant, whereas no response could be detected in visna-infected sheep. Complement-fixing antibody titers to basic protein and to a lipid antigen of brain, probably galactocerebroside, rose briskly after sensitization. In visna-infected sheep there was no increase in either antibody. A large proportion of Hampshire and Icelandic sheep had low levels of complement-fixing antibody to CNS antigens prior to induction of EAE or infection with visna virus [C-type virus]. The origin of this antibody is undetermined, but it appeared to have no effect on the course of either disease. Immunosuppression of sheep with antilymphoid serum prevented induction of EAE. Acute EAE was successfully induced in sheep and used as a model to measure immune responses to CNS antigens and as an index of immunosuppression. These comparative studies did not provide any evidence for the role of an autoimmune response to the 2 CNS system antigens tested in the pathogenesis of visna.