factors downregulate the suppression. Disruption of the loop leads to hyperreactivity, regulation can modify the strength of the immune response. A related suggestion with regard to interleukin 2 is that activated regulatory T cells take up interleukin 2 so avidly that they deprive effector T cells of sufficient to avoid apoptosis. A major mechanism of suppression by regulatory T cells is through the prevention of co-stimulation through CD28 on effector T cells by the action of the molecule CTLA-4. Induced regulatory T cells Induced regulatory T (iTreg) cells (CD4+ CD25+ FOXP3+) are suppressive cells involved in tolerance. iTreg cells have been shown to suppress T cell proliferation and experimental autoimmune diseases. These cells include Treg17 cells. iTreg cells develop from mature CD4+ conventional T cells outside of the thymus: a defining distinction between natural regulatory T (nTreg) cells and iTreg cells. Though iTreg and nTreg cells share a similar function iTreg cells have recently been shown to be "an essential non-redundant regulatory subset that supplements nTreg cells, in part by expanding TCR diversity within regulatory responses". Acute depletion of the iTreg cell pool in mouse models has resulted in inflammation and weight loss. The contribution of nTreg cells versus iTreg cells in maintaining tolerance is unknown, but both are important. Epigenetic differences have been observed between nTreg and iTreg cells, with the former having more stable FOXP3 expression and wider demethylation. The small intestinal environment is high in vitamin A and is a location where retinoic acid is produced. The retinoic acid and TGF-beta produced by dendritic cells within this area signal for production of regulatory T cells. Vitamin A and TGF-beta promote T cell differentiation into regulatory T cells opposed to Th17 cells, even in the presence of IL-6. The intestinal environment can lead to induced regulatory T cells with TGF-beta and retinoic acid, some of which express the lectin-like receptor CD161 and are specialized to maintain barrier integrity by accelerating wound healing. The Tregs within the gut are differentiated from naïve T cells after antigen is introduced. It has recently been shown that human regulatory T cells can be induced from both naive and pre-committed Th1 cells and Th17 cells using a parasite-derived TGF-β mimic, secreted by Heligmosomoides polygyrus and termed Hp-TGM (H. polygyrus TGF-β mimic). Hp-TGM can induce murine FOXP3 expressing regulatory T cells that were stabile in presence of inflammation in vivo. Hp-TGM-induced human FOXP3+ regulatory