Regulatory T cells play a role in T-cell receptor CDR2 peptide regulation of experimental autoimmune encephalomyelitis

Abigail C. Buenafe, Shayne Andrew, Halina Offner, Arthur A. Vandenbark

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Eliciting T-cell receptor (TCR) -specific responsiveness has been known to provide an effective autoregulatory mechanism for limiting inflammation mediated by T effector cells. Our previous use of TCR peptides derived from the CDR3 regions of a pathogenic TCR effectively reversed ongoing experimental autoimmune encephalomyelitis (EAE) in a humanized TCR transgenic model. In this study, we use the TCR BV8S2 CDR2 peptide in the non-transgenic C57BL/6 EAE model to down-regulate the heterogeneous TCR BV8S2 +MOG-35-55-specific pathogenic T-cell population and demonstrate successful treatment of EAE after disease onset. Suppression of disease was associated with reduced MOG-35-55-specific and non-specific T-cell production of interleukin-17a and interferon-γ in the central nervous system, as well as reduced numbers of CD4 + and Foxp3 + T cells in the central nervous system. With the use of Foxp3-GFP and Foxp3 conditional knockout mice, we demonstrate that the TCR CDR2 peptide treatment effect is dependent on the presence of Foxp3 + regulatory T cells and that regulatory T cell numbers are significantly expanded in the periphery of treated mice. Hence, TCR CDR2 peptide therapy is effective in regulating heterogeneous, pathogenic T-cell populations through the activity of the Foxp3 + regulatory T cell population.

Original languageEnglish (US)
Pages (from-to)168-179
Number of pages12
JournalImmunology
Volume135
Issue number2
DOIs
StatePublished - Feb 1 2012

Keywords

  • Encephalitis
  • Encephalomyelitis
  • Experimental autoimmune encephalomyelitis
  • Immunotherapy
  • Regulatory T cells
  • T-cell receptor
  • Therapy

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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