IFN‐γ Triggered STAT1‐PKB/AKT Signalling Pathway Influences the Function of Alloantigen Reactive Regulatory T Cells

Abstract

(current address) * Corresponding authors: Kathryn J. Wood, kathryn.wood@nds.ox.ac.uk; Bin Wei, weibin@sibs.ac.cn

IFN-γ Production by Allogeneic Foxp3+ Regulatory T Cells Is Essential for Preventing Experimental Graft-versus-Host Disease

“…In contrast, effective inhibition of alloresponses seems to depend on alloantigen-specific Treg cells (6,34). It is now emerging that IFN-g production by natural Treg cells can be important for their suppressive function in transplantation by autocrine activation through IFN-g receptor signaling (35). Such autocrine activation may also explain why it is so important that IFN-g is produced by the Treg cells themselves to inhibit acute GVHD.…”

Induction of antigen specific CD4+CD25+Foxp3+T regulatory cells from naïve natural thymic derived T regulatory cells

“…IFN-γ acts on activated Treg to induce STAT1, which in turn induces t-bet and IFN-γ expression [120,121].…”

CD4+CD25+Foxp3+IFN-γ+ human induced T regulatory cells are induced by interferon-γ and suppress alloresponses nonspecifically

“…In mice, a subpopulation of Tregs was described that produced IFN-␥ after phorbol 12-myristate 13-acetate (PMA)/ionomycin stimulation [5]. Murine IFN-␥-producing Tregs inhibited skin graft rejection, whereas Tregs generated in IFN-␥-deficient mice as well as Tregs deficient of the IFN-␥ receptor exhibited impaired suppressive function and ability to control skin graft rejection [6,7]. It was demonstrated that the inhibition of skin graft rejection was mediated by the IFN-␥-triggered STAT1-PKB/AKT signaling pathway [7].…”

“…It was demonstrated that the inhibition of skin graft rejection was mediated by the IFN-␥-triggered STAT1-PKB/AKT signaling pathway [7]. Furthermore, CD4 ϩ Foxp3 ϩ T cells of mice tolerized by pretreatment with donor alloantigen under the cover of anti-CD4 antibody produced significantly higher levels of IFN-␥ than CD4 ϩ Foxp3 ϩ T cells of naive animals [7]. Several authors reported on both IL-17 and IFN-␥ expression of induced or natural murine Treg [8 -11].…”

“…Murine IFN-␥-producing Tregs inhibited skin graft rejection, whereas Tregs generated in IFN-␥-deficient mice as well as Tregs deficient of the IFN-␥ receptor exhibited impaired suppressive function and ability to control skin graft rejection [6,7]. It was demonstrated that the inhibition of skin graft rejection was mediated by the IFN-␥-triggered STAT1-PKB/AKT signaling pathway [7]. Furthermore, CD4 ϩ Foxp3 ϩ T cells of mice tolerized by pretreatment with donor alloantigen under the cover of anti-CD4 antibody produced significantly higher levels of IFN-␥ than CD4 ϩ Foxp3 ϩ T cells of naive animals [7].…”