Differentiation of type 1 T regulatory cells (Tr1) by tolerogenic DC-10 requires the IL-10-dependent ILT4/HLA-G pathway

Blood. 2010 Aug 12;116(6):935-44. doi: 10.1182/blood-2009-07-234872. Epub 2010 May 6.

Abstract

Type 1 T regulatory (Tr1) cells suppress immune responses in vivo and in vitro and play a key role in maintaining tolerance to self- and non-self-antigens. Interleukin-10 (IL-10) is the crucial driving factor for Tr1 cell differentiation, but the molecular mechanisms underlying this induction remain unknown. We identified and characterized a subset of IL-10-producing human dendritic cells (DCs), termed DC-10, which are present in vivo and can be induced in vitro in the presence of IL-10. DC-10 are CD14(+), CD16(+), CD11c(+), CD11b(+), HLA-DR(+), CD83(+), CD1a(-), CD1c(-), express the Ig-like transcripts (ILTs) ILT2, ILT3, ILT4, and HLA-G antigen, display high levels of CD40 and CD86, and up-regulate CD80 after differentiation in vitro. DC-10 isolated from peripheral blood or generated in vitro are potent inducers of antigen-specific IL-10-producing Tr1 cells. Induction of Tr1 cells by DC-10 is IL-10-dependent and requires the ILT4/HLA-G signaling pathway. Our data indicate that DC-10 represents a novel subset of tolerogenic DCs, which secrete high levels of IL-10, express ILT4 and HLA-G, and have the specific function to induce Tr1 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Communication / immunology
  • Cell Differentiation / immunology
  • Dendritic Cells / cytology*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Flow Cytometry
  • Gene Expression / immunology
  • HLA Antigens / genetics
  • HLA Antigens / immunology
  • HLA Antigens / metabolism*
  • HLA-G Antigens
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class I / metabolism*
  • Humans
  • Immune Tolerance / immunology*
  • Immunophenotyping
  • Interleukin-10 / immunology
  • Interleukin-10 / metabolism*
  • Interleukin-12 / metabolism
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology
  • Membrane Glycoproteins / metabolism*
  • Monocytes / cytology
  • Monocytes / immunology
  • Monocytes / metabolism
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / immunology
  • Receptors, Immunologic / metabolism*
  • Signal Transduction / immunology
  • T-Lymphocytes, Regulatory / cytology*
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism

Substances

  • HLA Antigens
  • HLA-G Antigens
  • Histocompatibility Antigens Class I
  • IL10 protein, human
  • LILRB2 protein, human
  • Membrane Glycoproteins
  • Receptors, Immunologic
  • Interleukin-10
  • Interleukin-12