CD137 signaling interferes with activation and function of CD4 +CD25+ regulatory T cells in induced tolerance to experimental autoimmune thyroiditis

Gerald P. Morris, Lieping Chen, Yi Chi M Kong

Research output: Contribution to journalArticlepeer-review

Abstract

Experimental autoimmune thyroiditis (EAT), a model for Hashimoto's thyroiditis, is a T cell-mediated disease inducible with mouse thyroglobulin (mTg). Pretreatment with mTg, however, can induce CD4+ T cell-mediated tolerance to EAT. We demonstrate that CD4+CD25 + regulatory cells are critical for the tolerance induction, as in vivo depletion of CD25+ cells abrogated established tolerance, and CD4+CD25+ cells from tolerized mice suppressed mTg-responsive cells in vitro. Importantly, administration of an agonistic CD137 monoclonal antibody (mAb) inhibited tolerance development, and the mediation of established tolerance. CD137 mAb also inhibited the suppression of mTg-responsive cells by CD4+CD25+ cells in vitro. Signaling through CD137 likely resulted in enhancement of the responding inflammatory T cells, as anti-CD137 did not enable CD4+CD25 + T cells to proliferate in response to mTg in vitro.

Original languageEnglish (US)
Pages (from-to)20-29
Number of pages10
JournalCellular Immunology
Volume226
Issue number1
DOIs
StatePublished - Nov 2003
Externally publishedYes

Keywords

  • 4-1BB
  • Autoimmunity
  • CD137
  • CD25
  • Experimental autoimmune thyroiditis
  • Regulatory T cells

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

Fingerprint

Dive into the research topics of 'CD137 signaling interferes with activation and function of CD4 +CD25+ regulatory T cells in induced tolerance to experimental autoimmune thyroiditis'. Together they form a unique fingerprint.

Cite this