Prevention and treatment of experimental autoimmune encephalomyelitis with clonotypic CDR3 peptides

CD4+ FoxP3+ T-regulatory cells suppress interleukin-2-dependent expansion of myelin basic protein-specific T cells

Abigail C. Buenafe, Shayne Andrew, Michael Afentoulis, Halina Offner, Arthur Vandenbark

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Summary T-cell receptor (TCR)-derived peptides are recognized by the immune system and are capable of modulating autoimmune responses. Using the myelin basic protein (MBP) TCR 1501 transgenic mouse model, we demonstrated that TCR CDR3 peptides from the transgenic TCR can provide a protective effect when therapy is initiated before the induction of experimental autoimmune encephalomyelitis (EAE). More importantly, TCR CDR3 peptide therapy can ameliorate the disease when administered after EAE onset. Concurrent with the therapeutic effects, we observed reduced T-cell proliferation and reduced interleukin-2 (IL-2) levels in response to stimulation with MBP-85-99 peptide in splenocyte cultures from mice receiving TCR CDR3 peptides compared with that of control mice. Moreover, we found that Foxp3+ CD4 T cells from mice protected with TCR CDR3 peptide are preferentially expanded in the presence of IL-2. This is supportive of a proposed mechanism where Foxp3+ T-regulatory cells induced by therapy with MBP-85-99 TCR CDR3 peptides limit expansion and the encephalitogenic activity of MBP-85-99-specific T cells by regulating the levels of secreted IL-2.

Original languageEnglish (US)
Pages (from-to)114-124
Number of pages11
JournalImmunology
Volume130
Issue number1
DOIs
StatePublished - May 2010

Fingerprint

Myelin Basic Protein
Autoimmune Experimental Encephalomyelitis
Regulatory T-Lymphocytes
T-Cell Antigen Receptor
Interleukin-2
T-Lymphocytes
Peptides
Therapeutics
Peptide T
Therapeutic Uses
Cell- and Tissue-Based Therapy
Autoimmunity
Transgenic Mice
Immune System
Cell Proliferation

Keywords

  • Experimental autoimmune encephalomyelitis (EAE)
  • Foxp3
  • T regulatory (Treg)
  • T-cell receptor (TCR) peptide
  • Therapy

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

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title = "Prevention and treatment of experimental autoimmune encephalomyelitis with clonotypic CDR3 peptides: CD4+ FoxP3+ T-regulatory cells suppress interleukin-2-dependent expansion of myelin basic protein-specific T cells",
abstract = "Summary T-cell receptor (TCR)-derived peptides are recognized by the immune system and are capable of modulating autoimmune responses. Using the myelin basic protein (MBP) TCR 1501 transgenic mouse model, we demonstrated that TCR CDR3 peptides from the transgenic TCR can provide a protective effect when therapy is initiated before the induction of experimental autoimmune encephalomyelitis (EAE). More importantly, TCR CDR3 peptide therapy can ameliorate the disease when administered after EAE onset. Concurrent with the therapeutic effects, we observed reduced T-cell proliferation and reduced interleukin-2 (IL-2) levels in response to stimulation with MBP-85-99 peptide in splenocyte cultures from mice receiving TCR CDR3 peptides compared with that of control mice. Moreover, we found that Foxp3+ CD4 T cells from mice protected with TCR CDR3 peptide are preferentially expanded in the presence of IL-2. This is supportive of a proposed mechanism where Foxp3+ T-regulatory cells induced by therapy with MBP-85-99 TCR CDR3 peptides limit expansion and the encephalitogenic activity of MBP-85-99-specific T cells by regulating the levels of secreted IL-2.",
keywords = "Experimental autoimmune encephalomyelitis (EAE), Foxp3, T regulatory (Treg), T-cell receptor (TCR) peptide, Therapy",
author = "Buenafe, {Abigail C.} and Shayne Andrew and Michael Afentoulis and Halina Offner and Arthur Vandenbark",
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T1 - Prevention and treatment of experimental autoimmune encephalomyelitis with clonotypic CDR3 peptides

T2 - CD4+ FoxP3+ T-regulatory cells suppress interleukin-2-dependent expansion of myelin basic protein-specific T cells

AU - Buenafe, Abigail C.

AU - Andrew, Shayne

AU - Afentoulis, Michael

AU - Offner, Halina

AU - Vandenbark, Arthur

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N2 - Summary T-cell receptor (TCR)-derived peptides are recognized by the immune system and are capable of modulating autoimmune responses. Using the myelin basic protein (MBP) TCR 1501 transgenic mouse model, we demonstrated that TCR CDR3 peptides from the transgenic TCR can provide a protective effect when therapy is initiated before the induction of experimental autoimmune encephalomyelitis (EAE). More importantly, TCR CDR3 peptide therapy can ameliorate the disease when administered after EAE onset. Concurrent with the therapeutic effects, we observed reduced T-cell proliferation and reduced interleukin-2 (IL-2) levels in response to stimulation with MBP-85-99 peptide in splenocyte cultures from mice receiving TCR CDR3 peptides compared with that of control mice. Moreover, we found that Foxp3+ CD4 T cells from mice protected with TCR CDR3 peptide are preferentially expanded in the presence of IL-2. This is supportive of a proposed mechanism where Foxp3+ T-regulatory cells induced by therapy with MBP-85-99 TCR CDR3 peptides limit expansion and the encephalitogenic activity of MBP-85-99-specific T cells by regulating the levels of secreted IL-2.

AB - Summary T-cell receptor (TCR)-derived peptides are recognized by the immune system and are capable of modulating autoimmune responses. Using the myelin basic protein (MBP) TCR 1501 transgenic mouse model, we demonstrated that TCR CDR3 peptides from the transgenic TCR can provide a protective effect when therapy is initiated before the induction of experimental autoimmune encephalomyelitis (EAE). More importantly, TCR CDR3 peptide therapy can ameliorate the disease when administered after EAE onset. Concurrent with the therapeutic effects, we observed reduced T-cell proliferation and reduced interleukin-2 (IL-2) levels in response to stimulation with MBP-85-99 peptide in splenocyte cultures from mice receiving TCR CDR3 peptides compared with that of control mice. Moreover, we found that Foxp3+ CD4 T cells from mice protected with TCR CDR3 peptide are preferentially expanded in the presence of IL-2. This is supportive of a proposed mechanism where Foxp3+ T-regulatory cells induced by therapy with MBP-85-99 TCR CDR3 peptides limit expansion and the encephalitogenic activity of MBP-85-99-specific T cells by regulating the levels of secreted IL-2.

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