Cutting edge: induction of B7-H4 on APCs through IL-10: novel suppressive mode for regulatory T cells

J Immunol. 2006 Jul 1;177(1):40-4. doi: 10.4049/jimmunol.177.1.40.

Abstract

Multiple modes of suppressive mechanisms including IL-10 are thought to be implicated in CD4+CD25+ regulatory T (Treg) cell-mediated suppression. However, the cellular source, role, and molecular mechanism of IL-10 in Treg cell biology remain controversial. We now studied the interaction between Treg cells and APCs. We demonstrate that Treg cells, but not conventional T cells, trigger high levels of IL-10 production by APCs, stimulate APC B7-H4 expression, and render APCs immunosuppressive. Initial blockade of B7-H4 reduces the suppressive activity mediated by Treg cell-conditioned APCs. Further, APC-derived, rather than Treg cell-derived, IL-10 is responsible for APC B7-H4 induction. Therefore, Treg cells convey suppressive activity to APCs by stimulating B7-H4 expression through IL-10. Altogether, our data provide a novel cellular and molecular mechanism for Treg cell-mediated immunosuppression at the level of APCs, and suggest a plausible mechanism for the suppressive effect of IL-10 in Treg cell-mediated suppression.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies, Blocking / pharmacology
  • Antigen-Presenting Cells / immunology*
  • Antigen-Presenting Cells / metabolism*
  • B7-1 Antigen / biosynthesis*
  • B7-1 Antigen / genetics
  • B7-1 Antigen / immunology
  • B7-1 Antigen / physiology
  • Cells, Cultured
  • Coculture Techniques
  • Down-Regulation / genetics
  • Down-Regulation / immunology*
  • Female
  • Humans
  • Interleukin-10 / biosynthesis
  • Interleukin-10 / deficiency
  • Interleukin-10 / genetics
  • Interleukin-10 / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism*
  • Up-Regulation / genetics
  • Up-Regulation / immunology
  • V-Set Domain-Containing T-Cell Activation Inhibitor 1

Substances

  • Antibodies, Blocking
  • B7-1 Antigen
  • V-Set Domain-Containing T-Cell Activation Inhibitor 1
  • VTCN1 protein, human
  • Interleukin-10