Interleukin-12 converts Foxp3+ regulatory T cells to interferon-?-producing Foxp3+ T cells that inhibit colitis.

ABSTRACT: Regulatory T (Treg) cells are plastic, but the in vivo mechanisms by which they are converted into foxhead box p3 (Foxp3+) interferon (IFN)-?+ T cells and whether these converted cells retain the ability to inhibit colitis are not clear.Foxp3+ Treg cells were generated by culture of naïve CD4+ T cells from Foxp3GFP CBir1 T-cell receptor (TCR) transgenic (Tg) (CBir1-Tg) mice, which are specific for CBir1 flagellin (an immunodominant microbiota antigen), with transforming growth factor-?. Foxp3GFP+ CBir1-Tg Treg cells were isolated by fluorescence-activated cell sorting and transferred into TCR?x?-/- mice. Colitis was induced by transfer of naïve CBir1-Tg CD4+ T cells into immunodeficient mice.Microbiota antigen-specific Foxp3+ Treg cells were converted, in the intestine, to IFN-?+ T-helper (Th)1 cells, interleukin (IL)-17+ Th17 cells, and Foxp3+ T cells that coexpress IFN-? and/or IL-17. Conversion of Treg cells into IFN-?-producing Th1 cells and Foxp3+IFN-?+ T cells required innate cell production of IL-12 in the intestine; blocking IL-12 with an antibody inhibited their conversion to Th1 and Foxp3+IFN-?+ T cells in the intestines of mice that were recipients of Treg cells. Addition of IL-12, but not IL-23, promoted conversion of Treg cells into Th1 and Foxp3+IFN-?+ T cells, in vitro. Foxp3+IFN-?+ T cells had regulatory activity because they suppressed proliferation of naïve T cells, in vitro, and inhibited induction of colitis by microbiota antigen-specific T cells. IFN-?+ Th1 cells were not converted into Treg cells; Foxp3+IFN-?+ T cells differentiated into IFN-?+ but not Foxp3+ T cells.IL-12 promotes conversion of Treg cells into IFN-?-expressing cells; Foxp3+IFN-?+ T cells retain their regulatory functions and develop during the transition of Foxp3+ Treg cells into IFN-?+ Th1 cells.

SUBMITTER: Feng T 

PROVIDER: S-EPMC3109200 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature