Antigen-Specific Down-Regulation of Myelin Basic Protein-Reactive T Cells During Spontaneous Recovery From Experimental Autoimmune Encephalomyelitis: Further Evidence of Apoptotic Deletion of Autoreactive T Cells in the Central Nervous System

Tabi, Zsuzsanna, McCombe, Pamela A. and Pender, Michael P. (1995) Antigen-Specific Down-Regulation of Myelin Basic Protein-Reactive T Cells During Spontaneous Recovery From Experimental Autoimmune Encephalomyelitis: Further Evidence of Apoptotic Deletion of Autoreactive T Cells in the Central Nervous System. International Immunology, 7 6: 967-973.

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Author Tabi, Zsuzsanna
McCombe, Pamela A.
Pender, Michael P.
Title Antigen-Specific Down-Regulation of Myelin Basic Protein-Reactive T Cells During Spontaneous Recovery From Experimental Autoimmune Encephalomyelitis: Further Evidence of Apoptotic Deletion of Autoreactive T Cells in the Central Nervous System
Journal name International Immunology   Check publisher's open access policy
Publication date 1995-01-01
Sub-type Article
Volume number 7
Issue number 6
ISSN 0953-8178
Start page 967
End page 973
Total pages 7
Language eng
Subject 320702 Central Nervous System
321013 Neurology and Neuromuscular Diseases
Abstract Experimental autoimmune encephalomyelitis (EAE) was induced in Lewis rats by the i.v. injection of 107 cloned V beta 8.2+ T cells specific for the 72-89 peptide of guinea pig myelin basic protein (MBP). Some animals were injected simultaneously with 107 cloned T cells specific for ovalbumin (OVA). Lymphocytes were isolated from the spinal cord and from the peripheral lymphoid organs of these rats and the frequencies of MBP-peptide-specific or OVA-specific proliferating cells were estimated by limiting dilution analysis at different times after cell transfer. The frequencies of cells specific for MBP_72-89 or OVA in the spinal cord were highest 5 days after cell transfer (MBP_72-89, 1 in 1149; OVA, 1 in 1116). On day 7, when the rats were recovering, the frequency of cells specific for MBP_72-89 in the spinal cord fell dramatically to <1 in 105, while that of OVA-specific cells decreased to a much lesser extent (1 in 7001). The frequencies of MBP_72-89-specific cells in the peripheral lymphoid organs during and after recovery were also much lower than those of OVA-specific cells. A similar pattern of down-regulation of the MBP-peptide-specific, but not the OVA-specific, T cell response was observed in the spleen and mesenteric lymph nodes (MLN) of rats 38 days after the active induction of EAE by immunization with equal amounts of MBP and OVA in adjuvants. In the passively transferred model, cells isolated from the spinal cord and MLN on day 7 did not regain responsiveness to MBP_72-89 after incubation with high levels of IL-2, indicating that the unresponsiveness was not due to T cell anergy. Thus this study demonstrates that there is a specific down-regulation of the MBP_72-89-specific T cell response during spontaneous recovery from EAE. This conclusion is consistent with our previous observation that V beta 8.2+ T cells are selectively eliminated from the CNS by apoptosis during recovery from EAE induced by the passive transfer of V beta 8.2+ T cells reactive to this MBP peptide. In contrast to autoreactive T cells, the non-autoreactive T cells that accumulate in the CNS during EAE appear to recirculate to the peripheral lymphoid organs.
Keyword apoptosis
experimental autoimmune encephalomyelitis
T cell deletion
tolerance
EAE
experimental allergic encephalomyelitis
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown
Additional Notes This is an author-produced PDF of an article later published as Zsuzsanna Tabi, Pamela A. McCombe and Michael P. Pender (1995) Antigen-Specific Down-Regulation of Myelin Basic Protein-Reactive T Cells During Spontaneous Recovery From Experimental Autoimmune Encephalomyelitis: Further Evidence of Apoptotic Deletion of Autoreactive T Cells in the Central Nervous System, International Immunology, 7 (6): 967-973. Copyright 1995 Oxford Journals. All rights reserved.

Document type: Journal Article
Sub-type: Article
Collection: School of Medicine Publications
 
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