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Chronic neurologic dysfunction and demyelination induced in lewis rats by repeated injections of encephalitogenic T‐lymphocyte lines
Author(s) -
Vandenbark A.A.,
Nilaver G.,
Konat G.,
Teal P.,
Offner H.
Publication year - 1986
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.490160406
Subject(s) - myelin basic protein , spinal cord , encephalomyelitis , myelin , gliosis , medicine , immunology , multiple sclerosis , lymphocyte , experimental autoimmune encephalomyelitis , central nervous system , pathology , endocrinology , psychiatry
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.