PARAMETERS OF CLINICAL RESISTANCE TO EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS

Abstract

Experimental autoimmune encephalomyelitis (EAE) is a model for delayed-type hypersensitivity and the inflammatory demyelinating diseases. Since variations in susceptibility to EAE occur, it has been suggested that resistance may be the result of an immunologic suppressor mechanism. Lymphocyte responses to EAE-associated antigens have been found to vary with susceptibility and resistance to EAE. These findings prompted us to examine the possibility that such variations may reflect different immunoregulatory mechanisms. The present study investigated the responsiveness of guinea pig lymphocytes to: (a) EAE-associated antigens, (b) T cell mitogens and (c) the effect of EAE-associated antigens on lymphocyte responses to these mitogens.;Random-bred Hartley, inbred Strain 2 and Strain 13 guinea pigs were inoculated for EAE. Sixty-six percent (69/103) of the Hartleys developed signs of EAE while the remaining 34% (34/103) were resistant. None of the Strain 2 and all of the Strain 13 guinea pigs developed EAE. Histological examination of nervous tissue revealed that susceptible Hartleys, Strain 13 and all of the Strain 2 animals had lesions characteristic of EAE. Tissue from resistant Hartleys showed fewer and less severe changes.;A lymphocyte transformation assay used to measure the responses of lymphocytes to the antigens and mitogens revealed four different sets of responses in vitro: (1) lymphocytes from all animals tested responded to the mitogens; (2) lymphocytes from susceptible animals responded to EAE-antigens; (3) lymphocytes from only resistant Hartleys were inhibited from responding to the mitogens by EAE-antigens; and (4) this inhibition was found to be specific as only EAE-associated antigens were capable of its induction.;Although lymphocytes from resistant Hartleys did not respond to EAE-antigens in the transformation assay, the finding of antigen-induced inhibition of mitogen responses suggested that the animals were sensitized to EAE-antigens. To corroborate that resistant Hartleys were sensitized, other immunologic parameters were examined. Plasmas from all EAE-sensitized animals had equivalent anti-EAE antigen antibody titers. Skin testing also showed that all EAE-inoculated Hartleys were sensitized.;These experiments documented that resistance and reduced histological changes characteristic of EAE correlated with a disease-specific antigen-induced inhibition of lymphocyte responses to T cell mitogens. These data suggest that clinical resistance to EAE in Hartley guinea pigs is mediated by an immunologic suppressor mechanism possibly requiring a disease-related antigen for its activation.