Regulatory T cells form stable and long-lasting cell cluster with myeloid dendritic cells (DC)

Int Immunol. 2012 Jul;24(7):417-26. doi: 10.1093/intimm/dxs039. Epub 2012 Feb 24.

Abstract

Regulatory T cells (Treg) with the capacity to suppress T-cell proliferation exert various effects on T cell function. In addition, Treg have been shown to modulate the phenotype and function of antigen-presenting cells (APC) including dendritic cells (DC), B cells and monocytes/macrophages. However, the specific mechanism(s) of how Treg affect APC have not been entirely identified so far. In this study, we analyzed the interaction of human Treg and effector T cells (Teff) with peripheral blood myeloid and monocyte-derived dendritic cells in vitro. A strong tendency for cell cluster formation between Treg and DC was observed, which was dependent on the adhesion molecules ICAM-1, LFA-3 and ICAM-3. In addition, Treg were found to express higher levels of LFA-1, LFA-2, LFA-3 and ICAM-3 both before and after activation with anti-CD3 antibodies. Using in vitro live cell imaging, we were further able to show that Treg-DC cell clusters, in contrast to Teff-DC clusters, were stable and long lasting. Co-cultures of DC with Treg diminished the up-regulation of activation induced costimulatory molecule expression on DC, and further reduced the production of tumor necrosis factor alpha and stimulated the production of IL-4. In summary, our data indicate that Treg-DC cluster formation might enable Treg to modulate phenotypic and functional characteristics of DC and help to constrain Teff activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Adhesion Molecules / metabolism*
  • Cell Communication / immunology*
  • Cell Differentiation
  • Cells, Cultured
  • Coculture Techniques
  • Dendritic Cells / immunology*
  • Humans
  • Immune Tolerance
  • Interleukin-4 / genetics
  • Interleukin-4 / metabolism
  • Monocytes / immunology
  • Myeloid Cells / immunology*
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes, Regulatory / immunology*
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Cell Adhesion Molecules
  • Tumor Necrosis Factor-alpha
  • Interleukin-4