Human CD4+ T cells express TLR5 and its ligand flagellin enhances the suppressive capacity and expression of FOXP3 in CD4+CD25+ T regulatory cells

J Immunol. 2005 Dec 15;175(12):8051-9. doi: 10.4049/jimmunol.175.12.8051.

Abstract

Germline encoded pattern recognition receptors, such as TLRs, provide a critical link between the innate and adaptive immune systems. There is also evidence to suggest that pathogen-associated molecular patterns may have the capacity to modulate immune responses via direct effects on CD4+ T cells. Given the key role of both CD4+CD25+ T regulatory (Treg) cells and the TLR5 ligand flagellin in regulating mucosal immune responses, we investigated whether TLR5 may directly influence T cell function. We found that both human CD4+CD25+ Treg and CD4+CD25- T cells express TLR5 at levels comparable to those on monocytes and dendritic cells. Costimulation of effector T cells with anti-CD3 and flagellin resulted in enhanced proliferation and production of IL-2, at levels equivalent to those achieved by costimulation with CD28. In contrast, costimulation with flagellin did not break the hyporesponsiveness of CD4+CD25+ Treg cells, but rather, potently increased their suppressive capacity and enhanced expression of FOXP3. These observations suggest that, in addition to their APC-mediated indirect effects, TLR ligands have the capacity to directly regulate T cell responses and modulate the suppressive activity of Treg cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • CD3 Complex / immunology
  • CD4-Positive T-Lymphocytes / chemistry
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / physiology*
  • Flagellin / pharmacology*
  • Forkhead Transcription Factors / genetics*
  • Humans
  • Interleukin-2 / biosynthesis
  • Receptors, Interleukin-2
  • T-Lymphocytes, Regulatory / chemistry
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / metabolism*
  • Toll-Like Receptor 5 / analysis
  • Toll-Like Receptor 5 / physiology*
  • Up-Regulation / drug effects

Substances

  • Antibodies, Monoclonal
  • CD3 Complex
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Interleukin-2
  • Receptors, Interleukin-2
  • TLR5 protein, human
  • Toll-Like Receptor 5
  • Flagellin