Neonatal injection of Lewis rats with recombinant Vβ8.2 induces T cell but not B cell tolerance and increased severity of experimental autoimmune encephalomyelitis

M. Vainiene, G. G. Burrows, K. Ariail, I. Robey, Arthur Vandenbark, Halina Offner

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Abstract

In Lewis rats with experimental autoimmune encephalomyelitis (EAE) mediated by Vβ8.2 effector cells, anti-idiotypic T cells and antibodies could be boosted by injection of Vβ8.2 peptides, inducing both T cells and antibodies that reduced the severity and shortened the course of disease. However, EAE in Lewis rats is self-limiting, and we sought to determine if the anti-idiotypic response contributed to the natural recovery process. In a previous study, we found that adult tolerance induced to one of the regulatory idiotopes, Vβ8.2-44-54, caused worsening of EAE, implicating response to this epitope in recovery from EAE. However, neonatally-induced tolerance to Vβ8.2-44-54 did not alter the course of EAE, suggesting either compensation by additional Vβ8.2 determinants, or mechanistic differences in tolerization protocols. In this report, we reevaluate the role of Vβ8.2 determinants in recovery from EAE, using two recombinant Vβ8.2 constructs to induce neonatal tolerance to the comprehensive set of Vβ8.2 epitopes prior to adult induction of EAE. We found that neonatal exposure to either of the recombinant Vβ8.2 molecules induced 'split' tolerance - specific T cell tolerance but enhanced antibody responses and a more severe course of EAE. In contrast, neonatal exposure to a Vβ8.2+ T cell hybridoma or a control protein did not induce T cell tolerance to Vβ8.2 determinants and did not alter the EAE disease course. These results are consistent with those obtained by inducing adult tolerance, and suggest that our previous result (normal recovery from EAE in rats neonatally tolerized to Vβ8.2-44-54) was probably due to a compensatory response to other Vβ8.2 determinants. In both studies, the data clearly implicate T cell recognition of Vβ8.2 determinants in the natural EAE recovery process.

Original languageEnglish (US)
Pages (from-to)475-486
Number of pages12
JournalJournal of Neuroscience Research
Volume45
Issue number4
DOIs
StatePublished - 1996

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Autoimmune Experimental Encephalomyelitis
B-Lymphocytes
T-Lymphocytes
Injections
Epitopes
Antibodies
Hybridomas
Autoimmune Diseases
Antibody Formation
Peptides

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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title = "Neonatal injection of Lewis rats with recombinant Vβ8.2 induces T cell but not B cell tolerance and increased severity of experimental autoimmune encephalomyelitis",
abstract = "In Lewis rats with experimental autoimmune encephalomyelitis (EAE) mediated by Vβ8.2 effector cells, anti-idiotypic T cells and antibodies could be boosted by injection of Vβ8.2 peptides, inducing both T cells and antibodies that reduced the severity and shortened the course of disease. However, EAE in Lewis rats is self-limiting, and we sought to determine if the anti-idiotypic response contributed to the natural recovery process. In a previous study, we found that adult tolerance induced to one of the regulatory idiotopes, Vβ8.2-44-54, caused worsening of EAE, implicating response to this epitope in recovery from EAE. However, neonatally-induced tolerance to Vβ8.2-44-54 did not alter the course of EAE, suggesting either compensation by additional Vβ8.2 determinants, or mechanistic differences in tolerization protocols. In this report, we reevaluate the role of Vβ8.2 determinants in recovery from EAE, using two recombinant Vβ8.2 constructs to induce neonatal tolerance to the comprehensive set of Vβ8.2 epitopes prior to adult induction of EAE. We found that neonatal exposure to either of the recombinant Vβ8.2 molecules induced 'split' tolerance - specific T cell tolerance but enhanced antibody responses and a more severe course of EAE. In contrast, neonatal exposure to a Vβ8.2+ T cell hybridoma or a control protein did not induce T cell tolerance to Vβ8.2 determinants and did not alter the EAE disease course. These results are consistent with those obtained by inducing adult tolerance, and suggest that our previous result (normal recovery from EAE in rats neonatally tolerized to Vβ8.2-44-54) was probably due to a compensatory response to other Vβ8.2 determinants. In both studies, the data clearly implicate T cell recognition of Vβ8.2 determinants in the natural EAE recovery process.",
author = "M. Vainiene and Burrows, {G. G.} and K. Ariail and I. Robey and Arthur Vandenbark and Halina Offner",
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T1 - Neonatal injection of Lewis rats with recombinant Vβ8.2 induces T cell but not B cell tolerance and increased severity of experimental autoimmune encephalomyelitis

AU - Vainiene, M.

AU - Burrows, G. G.

AU - Ariail, K.

AU - Robey, I.

AU - Vandenbark, Arthur

AU - Offner, Halina

PY - 1996

Y1 - 1996

N2 - In Lewis rats with experimental autoimmune encephalomyelitis (EAE) mediated by Vβ8.2 effector cells, anti-idiotypic T cells and antibodies could be boosted by injection of Vβ8.2 peptides, inducing both T cells and antibodies that reduced the severity and shortened the course of disease. However, EAE in Lewis rats is self-limiting, and we sought to determine if the anti-idiotypic response contributed to the natural recovery process. In a previous study, we found that adult tolerance induced to one of the regulatory idiotopes, Vβ8.2-44-54, caused worsening of EAE, implicating response to this epitope in recovery from EAE. However, neonatally-induced tolerance to Vβ8.2-44-54 did not alter the course of EAE, suggesting either compensation by additional Vβ8.2 determinants, or mechanistic differences in tolerization protocols. In this report, we reevaluate the role of Vβ8.2 determinants in recovery from EAE, using two recombinant Vβ8.2 constructs to induce neonatal tolerance to the comprehensive set of Vβ8.2 epitopes prior to adult induction of EAE. We found that neonatal exposure to either of the recombinant Vβ8.2 molecules induced 'split' tolerance - specific T cell tolerance but enhanced antibody responses and a more severe course of EAE. In contrast, neonatal exposure to a Vβ8.2+ T cell hybridoma or a control protein did not induce T cell tolerance to Vβ8.2 determinants and did not alter the EAE disease course. These results are consistent with those obtained by inducing adult tolerance, and suggest that our previous result (normal recovery from EAE in rats neonatally tolerized to Vβ8.2-44-54) was probably due to a compensatory response to other Vβ8.2 determinants. In both studies, the data clearly implicate T cell recognition of Vβ8.2 determinants in the natural EAE recovery process.

AB - In Lewis rats with experimental autoimmune encephalomyelitis (EAE) mediated by Vβ8.2 effector cells, anti-idiotypic T cells and antibodies could be boosted by injection of Vβ8.2 peptides, inducing both T cells and antibodies that reduced the severity and shortened the course of disease. However, EAE in Lewis rats is self-limiting, and we sought to determine if the anti-idiotypic response contributed to the natural recovery process. In a previous study, we found that adult tolerance induced to one of the regulatory idiotopes, Vβ8.2-44-54, caused worsening of EAE, implicating response to this epitope in recovery from EAE. However, neonatally-induced tolerance to Vβ8.2-44-54 did not alter the course of EAE, suggesting either compensation by additional Vβ8.2 determinants, or mechanistic differences in tolerization protocols. In this report, we reevaluate the role of Vβ8.2 determinants in recovery from EAE, using two recombinant Vβ8.2 constructs to induce neonatal tolerance to the comprehensive set of Vβ8.2 epitopes prior to adult induction of EAE. We found that neonatal exposure to either of the recombinant Vβ8.2 molecules induced 'split' tolerance - specific T cell tolerance but enhanced antibody responses and a more severe course of EAE. In contrast, neonatal exposure to a Vβ8.2+ T cell hybridoma or a control protein did not induce T cell tolerance to Vβ8.2 determinants and did not alter the EAE disease course. These results are consistent with those obtained by inducing adult tolerance, and suggest that our previous result (normal recovery from EAE in rats neonatally tolerized to Vβ8.2-44-54) was probably due to a compensatory response to other Vβ8.2 determinants. In both studies, the data clearly implicate T cell recognition of Vβ8.2 determinants in the natural EAE recovery process.

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