Phenotypic and functional switch of macrophages induced by regulatory CD4+CD25+ T cells in mice.
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.
Transplantation Biology Research Division, State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Guangwei
G
Liu
Haixia
H
Ma
Lin
L
Qiu
Long
L
Li
Yuhong
Y
Cao
Jun
J
Ma
Yong
Y
Zhao
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D001119:Arginase / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D008822:Mice, Transgenic; D010587:Phagocytosis / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000276:immunology
D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D001119:Arginase