Rapid entry and downregulation of T Cells in the central nervous system During the reinduction of experimental autoimmune encephalomyelitis

Gordon, F. L., Nguyen, K. B., White, C. A. and Pender, M. P. (2001) Rapid entry and downregulation of T Cells in the central nervous system During the reinduction of experimental autoimmune encephalomyelitis. Journal of Neuroimmunology, 112 1-2: 15-27. doi:10.1016/S0165-5728(00)00341-6

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Author Gordon, F. L.
Nguyen, K. B.
White, C. A.
Pender, M. P.
Title Rapid entry and downregulation of T Cells in the central nervous system During the reinduction of experimental autoimmune encephalomyelitis
Journal name Journal of Neuroimmunology   Check publisher's open access policy
ISSN 0165-5728
Publication date 2001-01-01
Sub-type Article (original research)
DOI 10.1016/S0165-5728(00)00341-6
Open Access Status File (Author Post-print)
Volume 112
Issue 1-2
Start page 15
End page 27
Total pages 13
Editor Cedric S.Raine
C. F.Brosnan
Place of publication Amsterdam
Publisher Elsevier Science
Collection year 2001
Language eng
Subject 320702 Central Nervous System
320207 Autoimmunity
C1
730104 Nervous system and disorders
Abstract We investigated the mechanisms whereby a previous attack of experimental autoimmune encephalomyelitis (EAE) modifies a subsequent attack in the Lewis rat. Active immunization with myelin basic protein (MBP) and complete Freund's adjuvant 28 days after the passive transfer of MBP-sensitized spleen cells induced a second episode of EAE, which occurred earlier than in naive control animals, but was less severe overall. The pattern of neurological signs was also different in rechallenged rats, which had less severe tail and hindlimb weakness but more severe forelimb weakness. In rechallenged rats, inflammation was more severe in the cervical spinal cord, cerebellum, brainstem and cerebrum, but less severe in the lumbar spinal cord, than in controls. The early onset of EAE in rechallenged rats was explained by a memory T cell response to MBP72-89 in the draining lymph node and spleen, and by the enhanced entry of T cells into the central nervous system (CNS). However, the number of alpha beta T cells in the spinal cord of rechallenged rats declined faster than in controls, especially in the lumbosacral cord, where the number of V beta 8.2+ T cells and the frequency of T cells reactive to MBP72-89 rapidly decreased, indicating rapid downregulation of the immune response in the previously inflamed spinal cord. Apoptosis of inflammatory cells in the CNS was increased in the rechallenged rats and is likely to contribute to this downregulation. Furthermore, during the disease course the generation of encephalitogenic T cells in the peripheral lymphoid organs was limited compared with controls. Thus, a previous attack of EAE modifies a subsequent attack through the interaction of the following processes: a memory T cell response to MBP; facilitated T cell entry into the CNS; downregulation of the immune response in the CNS, including increased apoptosis of inflammatory cells; and a limited generation of encephalitogenic T cells in the peripheral lymphoid organs.
Keyword apoptosis
Resistance
Disease
Experimental Autoimmune Encephalomyelitis
Memory
T Cell
Tolerance
Experimental Allergic Encephalomyelitis
Myelin Basic-protein
Lewis Rats
Spontaneous-recovery
Mechanism
Lymphocytes
EAE
CNS
Demyelination
central nervous system
Q-Index Code C1
Additional Notes This is an author version of an article originally published as F. L. Gordon, K. B. Nguyen, C. A. White and M. P. Pender (2001) Rapid entry and downregulation of T cells in the central nervous system during the reinduction of experimental autoimmune encephalomyelitis. Journal of Neuroimmunology, 112 (1-2): 15-27. DOI: 10.1016/S0165-5728(00)00341-6 Copyright 2001 Elsevier. All rights reserved. Single copies only may be downloaded and printed for a user's personal research and study.

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 22 times in Thomson Reuters Web of Science Article | Citations
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Created: Thu, 01 Jul 2004, 10:00:00 EST