Phenotypic and functional switch of macrophages induced by regulatory CD4+CD25+ T cells in mice

Immunol Cell Biol. 2011 Jan;89(1):130-42. doi: 10.1038/icb.2010.70. Epub 2010 Jun 1.


CD4(+)CD25(+) regulatory T cells (Treg cells) are important in maintenance of peripheral tolerance. The direct effect of CD4(+)CD25(+) Treg cells on macrophages was studied using a mouse model in which syngeneic CD4(+)CD25(+) Treg cells were adoptively transferred into the peritoneal cavity of SCID mice. Peritoneal macrophages in mice transferred with CD4(+)CD25(+) Treg cells expressed significantly higher levels of CD23, CD47 and CD206 and less CD80 and major histocompatibility complex class II molecules as compared with those mice that received either CD4(+)CD25(-) T cells or no cells. Macrophages of mice injected with CD4(+)CD25(+) Treg cells displayed a remarkably enhanced phagocytosis of chicken red blood cells, and arginase activity together with an increased interleukin-10 (IL-10) production, whereas they showed a decreased antigen-presenting ability and nitric oxide production. Furthermore, CD4(+)CD25(+) Treg cells and CD4(+)CD25(-) T cells showed strong antagonistic effects on macrophage polarizations in vivo. Blocking arginase, IL-10 and/or transforming growth factor-β (TGF-β) partially but significantly reversed the effects of CD4(+)CD25(+) Treg cells to induce M2 macrophages in vivo suggesting that CD4(+)CD25(+) Treg cells have the ability to induce M2 macrophages at least in part through arginase, IL-10 and TGF-β pathways. Thus, we have provided the in vivo evidence to support the unknown pathways for CD4(+)CD25(+) Treg cells to regulate innate immunity by promoting the differentiation of M2 macrophages as well as by inhibiting M1 macrophage induction by CD4(+)CD25(-) T cells in mice. CD4(+)CD25(+) Treg cells efficiently induced M2 macrophage differentiation in mice, offering the in vivo evidence to support the role of CD4(+)CD25(+) Treg cells in regulating innate immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / immunology
  • Arginase / immunology
  • Arginase / metabolism
  • Cell Differentiation / immunology
  • Interleukin-10 / immunology
  • Macrophages / immunology*
  • Macrophages / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, SCID
  • Mice, Transgenic
  • Phagocytosis / immunology
  • Signal Transduction / immunology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism*
  • Transforming Growth Factor beta / immunology


  • Transforming Growth Factor beta
  • Interleukin-10
  • Arginase