CD49d is a new marker for distinct myeloid-derived suppressor cell subpopulations in mice

J Immunol. 2010 Jul 1;185(1):203-10. doi: 10.4049/jimmunol.0903573. Epub 2010 Jun 4.

Abstract

Myeloid-derived suppressor cells (MDSCs) are a heterogenous population of cells that negatively regulate the immune response during tumor progression, inflammation, and infection. In this study, through gene-expression analysis, we have identified a new marker, CD49d, which is expressed exclusively on CD11b(+)Gr-1(dull/int.) MDSCs. We have characterized two subpopulations of MDSCs based on CD49d expression in two different settings, a mouse model of inflammatory bowel disease and tumor-bearing mice. The CD49d(+) subset of MDSCs was mainly monocytic and strongly suppressed Ag-specific T cell proliferation in an NO-dependent mechanism similar to Gr-1(dull/int.) MDSCs. Alternatively, CD49d(-) cells were granulocytic and poorly inhibited T cell proliferation compared with CD11b(+)Gr-1(high) cells. Both mouse models showed preferential expansion of the granulocytic CD49d(-) subset. We suggest that CD49d can be used as an alternative marker for Gr-1 to differentiate between the subpopulations of MDSCs together with CD11b, which will ultimately help in understanding the mechanisms of immune suppression by MDSCs.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • CD11b Antigen / biosynthesis
  • CD11b Antigen / physiology
  • Cells, Cultured
  • Colorectal Neoplasms / immunology
  • Colorectal Neoplasms / pathology
  • Epitopes, T-Lymphocyte / immunology
  • Female
  • Immune Tolerance / immunology*
  • Immunophenotyping
  • Inflammatory Bowel Diseases / immunology
  • Inflammatory Bowel Diseases / pathology
  • Integrin alpha4 / biosynthesis
  • Integrin alpha4 / metabolism
  • Integrin alpha4 / physiology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Myeloid Cells / immunology*
  • Myeloid Cells / metabolism*
  • Myeloid Cells / pathology
  • Neoplasms, Experimental / immunology
  • Neoplasms, Experimental / pathology
  • Nitric Oxide / physiology
  • Receptors, Chemokine / biosynthesis
  • Receptors, Chemokine / physiology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocyte Subsets / pathology

Substances

  • Biomarkers
  • CD11b Antigen
  • Epitopes, T-Lymphocyte
  • Gr-1 protein, mouse
  • Receptors, Chemokine
  • Integrin alpha4
  • Nitric Oxide