CpG DNA inhibits CD4+CD25+ Treg suppression through direct MyD88-dependent costimulation of effector CD4+ T cells

Immunol Lett. 2007 Feb 15;108(2):183-8. doi: 10.1016/j.imlet.2006.12.007. Epub 2007 Jan 18.

Abstract

Toll-like receptor (TLR) ligands are notable for their ability to induce APC maturation, which in turn facilitates optimal T cell mediated immune responses. Toll-like receptor ligands, such as CpG DNA, can also modulate immune responses by blocking the suppressive effects of CD4+CD25+ regulatory T cells (Tregs). Recently, we have demonstrated that CpG DNA, in addition to its actions on APCs and Tregs, can provide direct costimulatory signals to CD4+CD25- T cells. Here we show that this costimulatory effect is sufficient to abrogate suppression by Tregs. These data indicate a previously undefined role for TLR ligands in directly modulating CD4+ T cell responses.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Animals
  • Antigen-Presenting Cells / immunology
  • CD4-Positive T-Lymphocytes / drug effects*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Proliferation / drug effects
  • Coculture Techniques
  • Forkhead Transcription Factors / metabolism
  • Immune Tolerance / drug effects
  • Immune Tolerance / immunology
  • Interleukin-2 / metabolism
  • Interleukin-2 / pharmacology
  • Interleukin-2 Receptor alpha Subunit / analysis
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myeloid Differentiation Factor 88 / deficiency
  • Myeloid Differentiation Factor 88 / genetics
  • Myeloid Differentiation Factor 88 / physiology*
  • Oligodeoxyribonucleotides / pharmacology*
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism

Substances

  • Adjuvants, Immunologic
  • CPG-oligonucleotide
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Interleukin-2
  • Interleukin-2 Receptor alpha Subunit
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • Oligodeoxyribonucleotides