medulla microenvironment, thus they are helping to the development of de novo Treg cells. High concentration of IL-1β caused by inflammation decrease de novo development of Treg cells in thymus. Binding of IL-1β to IL1R2 on the surface of Treg cells does not cause any signal transduction because there is no present Intracellular (TIR) Toll interleukin-1 receptor domain, which is normally present in innate immune cells. Function The immune system must be able to discriminate between self and non-self. When self/non-self discrimination fails, the immune system destroys cells and tissues of the body and as a result causes autoimmune diseases. Regulatory T cells actively suppress activation of the immune system and prevent pathological self-reactivity, i.e. autoimmune disease. The critical role regulatory T cells play within the immune system is evidenced by the severe autoimmune syndrome that results from a genetic deficiency in regulatory T cells (IPEX syndrome – see also below). The molecular mechanism by which regulatory T cells exert their suppressor/regulatory activity has not been definitively characterized and is the subject of intense research. In vitro experiments have given mixed results regarding the requirement of cell-to-cell contact with the cell being suppressed. The following represent some of the proposed mechanisms of immune suppression: Regulatory T cells produce a number of inhibitory cytokines. These include TGF-β, Interleukin 35, and Interleukin 10. It also appears that regulatory T cells can induce other cell types to express interleukin-10. Regulatory T cells can produce Granzyme B, which in turn can induce apoptosis of effector cells. Regulatory T cells from Granzyme B deficient mice are reported to be less effective suppressors of the activation of effector T cells. Reverse signalling through direct interaction with dendritic cells and the induction of immunosuppressive indoleamine 2,3-dioxygenase. Signalling through the ectoenzymes CD39 and CD73 with the production of immunosuppressive adenosine. Through direct interactions with dendritic cells by LAG3 and by TIGIT. This review of Treg interactions with dendritic cells provides distinction between mechanisms described for human cells versus mouse cells. Another control mechanism is through the IL-2 feedback loop. Antigen-activated T cells produce IL-2 which then acts on IL-2 receptors on regulatory T cells alerting them to the fact that high T cell activity is occurring in the region, and they mount a suppressory response against them. This is a negative feedback loop to ensure that overreaction is not occurring. If an actual infection is present other inflammatory