Blood Journal
Leading the way in experimental and clinical research in hematology

Myeloid-derived suppressor cells express the death receptor Fas and apoptose in response to T cell-expressed FasL

  1. Pratima Sinha1,
  2. Olesya Chornoguz1,
  3. Virginia K. Clements1,
  4. Konstantin A. Artemenko2,
  5. Roman A. Zubarev3, and
  6. Suzanne Ostrand-Rosenberg1,*
  1. 1 Department of Biological Sciences, University of Maryland Baltimore County, Baltimore, MD, United States;
  2. 2 Department of Physical & Analytical Chemistry, Uppsala University, Uppsala, Sweden;
  3. 3 Division of Molecular Biometry, Department of Medicinal Biochemistry & Biophysics, Karolinska Intitutet, Stockholm, Sweden
  1. * Corresponding author; email: srosenbe{at}umbc.edu

Abstract

Myeloid-derived suppressor cells (MDSC) inhibit adaptive and innate immunity and accumulate in the blood of individuals with cancer, chronic inflammation, trauma, infection, and stress. Some of the factors inducing their accumulation are known; however, mechanisms regulating their turn-over have not been identified. Mass spectrometry revealed prominent expression of apoptosis pathway proteins suggesting that MDSC turnover may be regulated by Fas-FasL-mediated apoptosis. This hypothesis was confirmed by demonstrating that blood MDSC induced by three mouse tumors were Fas+ and apoptosed in response to Fas agonist in vitro and to activated FasL+ T cells in vivo. FasL-deficient mice contained significantly more blood MDSC than FasL+/+ mice, and after removal of primary tumors MDSC regressed in STAT6-/- and CD1-/- mice, but not in STAT6-/-FasL-/- or CD1-/-FasL-/- mice. Fas+ macrophages and dendritic cells did not apoptose in response to activated T cells, indicating that Fas-FasL regulation of myeloid cells was restricted to MDSC. These results identify a new mechanism regulating MDSC levels in vivo, and demonstrate a retaliatory relationship between T cells and MDSC in that MDSC suppress T cell activation; however, once activated, T cells mediate MDSC apoptosis.

  • Submitted November 29, 2010.
  • Accepted March 18, 2011.