Immunoregulation of encephalitogenic MBP-NAc1-11-reactive T cells by CD4+ TCR-specific T cells involves IL-4, IL-10 and IFN-γ

Kirsten Adlard, Laura Tsaknaridis, Aaron Beam, Bruce F. Bebo, Arthur A. Vandenbark, Halina Offner

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

The generation of TCR transgenic (Tg) mice expressing a BV8S2 (Vβ8 subfamily 2) chain specific for the encephalitogenic NAc1-11 region of MBP provides a unique system for evaluating the mechanisms involved in anti-TCR immunoregulation of EAE. In a previous study, we showed that vaccination with BV8S2 protein induced specific T cells that inhibited proliferation responses and encephalitogenic activity of MBP-reactive T cells in vitro, and resulted in a skewed production of Th2 cytokines by the MBP-reactive T cells. These data suggested that regulation of the encephalitogenic T cells was mediated by inhibitory cytokines rather than through a deletional mechanism. In the current study, we have employed the BV8S2 Tg mouse model to address the issue of which cytokines produced by anti-TCR-reactive T cells can regulate the function of encephalitogenic Th1 cells. Utilizing neutralizing anti-cytokine antibodies to reverse inhibitory effects of supernatants from BV8S2-specific T cells, we found that IL-4, IL-10, and to a lesser extent, IFN-γ and TGF-β, were the major regulatory cytokines responsible for inhibiting encephalitogenic activity, proliferation, and IFN-γ secretion of MBP-NAc1-11-reactive Th1 cells. These results indicate that cytokine regulation is the major mechanism through which TCR specific CD4+ T cells regulate encephalitogenic and potentially other bystander Th1 cells.

Original languageEnglish (US)
Pages (from-to)237-248
Number of pages12
JournalAutoimmunity
Volume31
Issue number4
DOIs
StatePublished - Jan 1 1999

Keywords

  • Experimental autoimmune encephalomyelitis
  • Regulatory cytokines
  • TCR regulation
  • Transgenic mice

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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