Chronic neurologic dysfunction and demyelination induced in Lewis rats by repeated injections of encephalitogenic T-lymphocyte lines.
Experimental autoimmune encephalomyelitis (EAE) in the Lewis rat is characteristically a monophasic paralytic disorder. Recovered rats are thereafter immune to EAE induced by injection of guinea pig basic protein (GP-BP) in complete Freund's adjuvant (CFA), but they are still susceptible to EAE induced by an encephalitogenic T-lymphocyte line (BP-1). Induction of active EAE or injection of a sublethal dose of activated BP-1 cells resulted in a monophasic episode of EAE, followed by recovery of normal neurologic function. Repeated challenges with activated BP-1 cells, however, induced unremitting neurologic signs marked by loss of tail tonicity and incontinence, which persisted for more than 6 months. Histologically, the spinal cord of affected rats revealed attenuation of MBP staining (demyelination) and moderate-to-extensive gliosis associated with increased size of intervening spaces. Inflammatory cell lesions, however, were notably absent. Biophysical analysis of isolated spinal cord myelin from affected rats demonstrated a distorted distribution in subfraction densities and the appearance of extra-myelin proteins in the light myelin subfraction. Immunologically, chronically affected animals were unresponsive to the encephalitogenic determinant on GP-BP, although other BP determinants elicited strong delayed type hypersensitivity (DTH) reactions in rats immunized initially with GP-BP in CFA. These data show that ongoing neurologic dysfunction can be induced in the Lewis rat by a GP-BP specific T-lymphocyte line; they suggest that unremitting clinical signs can persist in the absence both of inflammatory lesions in the CNS and of pronounced immunologic responsiveness to the encephalitogenic determinant of GP-BP.
D000818:Animals; D002460:Cell Line; D002490:Central Nervous System / Q000473:pathology / Q000503:physiopathology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006168:Guinea Pigs; D006968:Hypersensitivity, Delayed; D007113:Immunity, Innate; D004676:Myelin Basic Protein / Q000276:immunology*; D009186:Myelin Sheath / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology*
D004676:Myelin Basic Protein