CD1d is a novel cell-surface marker for human monocytic myeloid-derived suppressor cells with T cell suppression activity in peripheral blood after allogeneic hematopoietic stem cell transplantation

Biochem Biophys Res Commun. 2018 Jan 1;495(1):519-525. doi: 10.1016/j.bbrc.2017.11.010. Epub 2017 Nov 3.

Abstract

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells that regulate immune responses in cancer and various pathological conditions. However, the phenotypic and functional heterogeneity of human MDSCs represents a major hurdle for the development of therapeutic strategies targeting or regulating MDSCs in tumor progression, inflammation, and graft-versus-host disease (GVHD). We previously shown that circulating HLA-DR-CD14+ monocytic MDSCs are a major contributor to clinical outcomes after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this study, we identified, using high-throughput screening, a set of surface markers that are strongly expressed in HLA-DR-CD14+ monocytic MDSCs isolated from the peripheral blood (PB) of patients receiving allo-HSCT. Subsequent experiments showed the consistent dominant expression of CD1d in monocytic MDSCs of allo-HSCT PB in comparison with granulocytic MDSCs. In addition, CD1d-expressing cells isolated from PB of allo-HSCT patients showed the suppressive activity of T cell proliferation and higher expression of MyD88 and IDO compared with CD1d- cells. Our results suggest that CD1d could be a valuable marker for further therapeutic evaluation of human monocytic MDSCs for immune-related diseases, including GVHD.

Keywords: Allogeneic HSCT; CD1d; MDSC; T cell suppression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD1d / analysis*
  • Antigens, CD1d / immunology
  • Cells, Cultured
  • Graft vs Host Disease / immunology
  • HLA-DR Antigens / analysis
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Lipopolysaccharide Receptors / analysis
  • Lipopolysaccharide Receptors / immunology
  • Lymphocyte Activation*
  • Monocytes / cytology
  • Monocytes / immunology
  • Myeloid-Derived Suppressor Cells / cytology
  • Myeloid-Derived Suppressor Cells / immunology*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • TWEAK Receptor / analysis
  • TWEAK Receptor / immunology
  • Transplantation, Homologous

Substances

  • Antigens, CD1d
  • CD1D protein, human
  • HLA-DR Antigens
  • Lipopolysaccharide Receptors
  • TWEAK Receptor