In vivo suppressive function of myeloid-derived suppressor cells is limited to the inflammatory site

Eur J Immunol. 2011 Mar;41(3):749-59. doi: 10.1002/eji.201041069. Epub 2011 Feb 2.


Current paradigms suggest that, despite the heterogeneity of myeloid-derived suppressor cells (MDSC), all Gr-1(+) CD11b(+) cells can exert suppressive function when exposed to inflammatory stimuli. In vitro evaluation shows that MDSC from multiple tissue sites have suppressive activity, and in vivo inhibition of MDSC enhances T-cell function; however, the relative capacity of MDSC present at localized inflammatory sites or in peripheral tissues to suppress T-cell responses in vivo has not been directly evaluated. In the current study, we observed that during a tissue-specific inflammatory response, MDSC inhibition of CD8(+) T-cell proliferation and IFN-γ production was restricted to the inflammatory site. Using a prostate-specific inflammatory model and a heterotopic prostate tumor model, we showed that MDSC from inflammatory sites or from tumor tissue possess immediate capacity to inhibit T-cell function, whereas those isolated from peripheral tissues (spleens and liver) were not suppressive without activation of iNOS by exposure to IFN-γ. These data suggest that MDSC are important regulators of immune responses in the prostate during acute inflammation and the chronic inflammatory setting of tumor growth, and that regulation of T-cell function by MDSC during a localized inflammatory response is restricted in vivo to the site of an ongoing immune response.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adoptive Transfer
  • Animals
  • Arginase / genetics
  • CD11b Antigen / metabolism
  • Cell Proliferation
  • Disease Models, Animal
  • Immune Tolerance*
  • Inflammation / genetics
  • Inflammation / immunology*
  • Inflammation / pathology
  • Male
  • Mice
  • Mice, Transgenic
  • Myeloid Cells / immunology*
  • Myeloid Cells / pathology
  • Nitric Oxide Synthase Type II / genetics
  • Ovalbumin / genetics
  • Ovalbumin / immunology
  • Phenotype
  • Prostatitis / genetics
  • Prostatitis / immunology
  • Prostatitis / pathology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Chemokine / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / pathology


  • CD11b Antigen
  • Gr-1 protein, mouse
  • RNA, Messenger
  • Receptors, Chemokine
  • Recombinant Proteins
  • Ovalbumin
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Arg1 protein, mouse
  • Arginase