Chronic neurologic dysfunction and demyelination induced in Lewis rats by repeated injections of encephalitogenic T-lymphocyte lines

Arthur Vandenbark, G. Nilaver, G. Konat, P. Teal, Halina Offner

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Abstract

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 of 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.

Original languageEnglish (US)
Pages (from-to)643-656
Number of pages14
JournalJournal of Neuroscience Research
Volume16
Issue number4
StatePublished - 1986

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Demyelinating Diseases
Neurologic Manifestations
Autoimmune Experimental Encephalomyelitis
Guinea Pigs
T-Lymphocytes
Injections
Freund's Adjuvant
Myelin Sheath
Proteins
Spinal Cord
Myelin Proteins
Gliosis
Delayed Hypersensitivity
Nervous System
Tail
Staining and Labeling

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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title = "Chronic neurologic dysfunction and demyelination induced in Lewis rats by repeated injections of encephalitogenic T-lymphocyte lines",
abstract = "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 of 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.",
author = "Arthur Vandenbark and G. Nilaver and G. Konat and P. Teal and Halina Offner",
year = "1986",
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journal = "Journal of Neuroscience Research",
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TY - JOUR

T1 - Chronic neurologic dysfunction and demyelination induced in Lewis rats by repeated injections of encephalitogenic T-lymphocyte lines

AU - Vandenbark, Arthur

AU - Nilaver, G.

AU - Konat, G.

AU - Teal, P.

AU - Offner, Halina

PY - 1986

Y1 - 1986

N2 - 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 of 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.

AB - 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 of 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.

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