Treatment of relapsing autoimmune encephalomyelitis with T cell receptor Vβ-specific antibodies when proteolipid protein is the autoantigen

Ruth Whitham, D. Wingett, J. Wineman, Michele Mass, K. Wegmann, Arthur Vandenbark, Halina Offner

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10 Citations (Scopus)

Abstract

Monoclonal antibodies (mAbs) directed against the Vβ chain of the T cell receptor (TCR) of pathogenic T cells have been used to treat acute murine experimental autoimmune encephalomyelitis (EAE) induced by myelin basic protein (BP). We evaluated anti-Vβ mAb for the treatment of relapsing EAE (R-EAE) induced in SJL/J mice by the myelin proteolipid protein (PLP) peptide 139-151. Spinal cord mononuclear cells isolated from mice immunized for R-EAE with PLP 139-151 were shown to express a predominance of Vβ2 and Vβ17 during acute and relapsing disease. T cell lines specific for PLP 139151 were magnetically sorted to express 80-90% Vβ2. These Vβ2-enriched lines induced typical relapsing demyelinating EAE in naive recipient mice. SJL/J mice with R-EAE induced by a PLP 139-151-specific T cell line expressing 88% Vβ2 were treated with anti-Vβ2 mAb. Anti-Vβ2 mAb markedly reduced clinical and histological disease severity when given at the time of cell transfer or when given at clinical disease onset. In contrast, anti-Vβ mAbs showed only a mild clinical effect on R-EAE induced by immunization with PLP 139-151 or R-EAE transferred by a PLP 139-151-specific T cell line expressing multiple Vβs. A cocktail of mAbs directed against Vβ2, Vβ4, and Vβ17 significantly reduced the numbers of spinal cord T cells expressing these Vβs during acute EAE but had little effect on disease course, suggesting that pathogenic T cells expressing other Vβs were producing disease. These findings may have implications for the treatment of multiple sclerosis with Vβ-selective therapy.

Original languageEnglish (US)
Pages (from-to)104-116
Number of pages13
JournalJournal of Neuroscience Research
Volume45
Issue number2
DOIs
StatePublished - 1996

Fingerprint

Proteolipids
Encephalomyelitis
Autoantigens
T-Cell Antigen Receptor
Autoimmune Experimental Encephalomyelitis
T-Lymphocytes
Antibodies
Proteins
Monoclonal Antibodies
Cell Line
Spinal Cord
Therapeutics
Myelin Basic Protein
Acute Disease
Multiple Sclerosis
Immunization
myelin proteolipid protein (139-151)
Peptides

Keywords

  • multiple sclerosis
  • T cell receptor antibodies
  • V region genes

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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title = "Treatment of relapsing autoimmune encephalomyelitis with T cell receptor Vβ-specific antibodies when proteolipid protein is the autoantigen",
abstract = "Monoclonal antibodies (mAbs) directed against the Vβ chain of the T cell receptor (TCR) of pathogenic T cells have been used to treat acute murine experimental autoimmune encephalomyelitis (EAE) induced by myelin basic protein (BP). We evaluated anti-Vβ mAb for the treatment of relapsing EAE (R-EAE) induced in SJL/J mice by the myelin proteolipid protein (PLP) peptide 139-151. Spinal cord mononuclear cells isolated from mice immunized for R-EAE with PLP 139-151 were shown to express a predominance of Vβ2 and Vβ17 during acute and relapsing disease. T cell lines specific for PLP 139151 were magnetically sorted to express 80-90{\%} Vβ2. These Vβ2-enriched lines induced typical relapsing demyelinating EAE in naive recipient mice. SJL/J mice with R-EAE induced by a PLP 139-151-specific T cell line expressing 88{\%} Vβ2 were treated with anti-Vβ2 mAb. Anti-Vβ2 mAb markedly reduced clinical and histological disease severity when given at the time of cell transfer or when given at clinical disease onset. In contrast, anti-Vβ mAbs showed only a mild clinical effect on R-EAE induced by immunization with PLP 139-151 or R-EAE transferred by a PLP 139-151-specific T cell line expressing multiple Vβs. A cocktail of mAbs directed against Vβ2, Vβ4, and Vβ17 significantly reduced the numbers of spinal cord T cells expressing these Vβs during acute EAE but had little effect on disease course, suggesting that pathogenic T cells expressing other Vβs were producing disease. These findings may have implications for the treatment of multiple sclerosis with Vβ-selective therapy.",
keywords = "multiple sclerosis, T cell receptor antibodies, V region genes",
author = "Ruth Whitham and D. Wingett and J. Wineman and Michele Mass and K. Wegmann and Arthur Vandenbark and Halina Offner",
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T1 - Treatment of relapsing autoimmune encephalomyelitis with T cell receptor Vβ-specific antibodies when proteolipid protein is the autoantigen

AU - Whitham, Ruth

AU - Wingett, D.

AU - Wineman, J.

AU - Mass, Michele

AU - Wegmann, K.

AU - Vandenbark, Arthur

AU - Offner, Halina

PY - 1996

Y1 - 1996

N2 - Monoclonal antibodies (mAbs) directed against the Vβ chain of the T cell receptor (TCR) of pathogenic T cells have been used to treat acute murine experimental autoimmune encephalomyelitis (EAE) induced by myelin basic protein (BP). We evaluated anti-Vβ mAb for the treatment of relapsing EAE (R-EAE) induced in SJL/J mice by the myelin proteolipid protein (PLP) peptide 139-151. Spinal cord mononuclear cells isolated from mice immunized for R-EAE with PLP 139-151 were shown to express a predominance of Vβ2 and Vβ17 during acute and relapsing disease. T cell lines specific for PLP 139151 were magnetically sorted to express 80-90% Vβ2. These Vβ2-enriched lines induced typical relapsing demyelinating EAE in naive recipient mice. SJL/J mice with R-EAE induced by a PLP 139-151-specific T cell line expressing 88% Vβ2 were treated with anti-Vβ2 mAb. Anti-Vβ2 mAb markedly reduced clinical and histological disease severity when given at the time of cell transfer or when given at clinical disease onset. In contrast, anti-Vβ mAbs showed only a mild clinical effect on R-EAE induced by immunization with PLP 139-151 or R-EAE transferred by a PLP 139-151-specific T cell line expressing multiple Vβs. A cocktail of mAbs directed against Vβ2, Vβ4, and Vβ17 significantly reduced the numbers of spinal cord T cells expressing these Vβs during acute EAE but had little effect on disease course, suggesting that pathogenic T cells expressing other Vβs were producing disease. These findings may have implications for the treatment of multiple sclerosis with Vβ-selective therapy.

AB - Monoclonal antibodies (mAbs) directed against the Vβ chain of the T cell receptor (TCR) of pathogenic T cells have been used to treat acute murine experimental autoimmune encephalomyelitis (EAE) induced by myelin basic protein (BP). We evaluated anti-Vβ mAb for the treatment of relapsing EAE (R-EAE) induced in SJL/J mice by the myelin proteolipid protein (PLP) peptide 139-151. Spinal cord mononuclear cells isolated from mice immunized for R-EAE with PLP 139-151 were shown to express a predominance of Vβ2 and Vβ17 during acute and relapsing disease. T cell lines specific for PLP 139151 were magnetically sorted to express 80-90% Vβ2. These Vβ2-enriched lines induced typical relapsing demyelinating EAE in naive recipient mice. SJL/J mice with R-EAE induced by a PLP 139-151-specific T cell line expressing 88% Vβ2 were treated with anti-Vβ2 mAb. Anti-Vβ2 mAb markedly reduced clinical and histological disease severity when given at the time of cell transfer or when given at clinical disease onset. In contrast, anti-Vβ mAbs showed only a mild clinical effect on R-EAE induced by immunization with PLP 139-151 or R-EAE transferred by a PLP 139-151-specific T cell line expressing multiple Vβs. A cocktail of mAbs directed against Vβ2, Vβ4, and Vβ17 significantly reduced the numbers of spinal cord T cells expressing these Vβs during acute EAE but had little effect on disease course, suggesting that pathogenic T cells expressing other Vβs were producing disease. These findings may have implications for the treatment of multiple sclerosis with Vβ-selective therapy.

KW - multiple sclerosis

KW - T cell receptor antibodies

KW - V region genes

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