Myeloid-derived suppressor cells from tumor-bearing mice impair TGF-β-induced differentiation of CD4+CD25+FoxP3+ Tregs from CD4+CD25-FoxP3- T cells

J Leukoc Biol. 2012 Nov;92(5):987-97. doi: 10.1189/jlb.0911465. Epub 2012 Aug 13.


MDSCs and Tregs play an essential role in the immunosuppressive networks that contribute to tumor-immune evasion. The mechanisms by which tumors promote the expansion and/or function of these suppressive cells and the cross-talk between MDSC and Treg remain incompletely defined. Previous reports have suggested that MDSC may contribute to Treg induction in cancer. Herein, we provide evidence that tumor-induced gr-MDSCs, endowed with the potential of suppressing conventional T Lc, surprisingly impair TGF-β1-mediated generation of CD4(+)CD25(+)FoxP3(+) iTregs. Furthermore, gr-MDSCs impede the proliferation of nTregs without, however, affecting FoxP3 expression. Suppression of iTreg differentiation from naïve CD4(+) cells by gr-MDSC occurs early in the polarization process, requires inhibition of early T cell activation, and depends on ROS and IDO but does not require arginase 1, iNOS, NO, cystine/cysteine depletion, PD-1 and PD-L1 signaling, or COX-2. These findings thus indicate that gr-MDSCs from TB hosts have the unanticipated ability to restrict immunosuppressive Tregs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Communication / immunology
  • Cell Differentiation / immunology*
  • Cell Separation
  • Female
  • Flow Cytometry
  • Forkhead Transcription Factors / immunology
  • Immune Tolerance / immunology*
  • Immunohistochemistry
  • Interleukin-2 Receptor alpha Subunit / immunology
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Myeloid Cells / immunology*
  • Neoplasms, Experimental / immunology*
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology
  • Transforming Growth Factor beta / metabolism
  • Tumor Escape / immunology*


  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Interleukin-2 Receptor alpha Subunit
  • Transforming Growth Factor beta