Regulatory T cells (Treg cells) suppress the activity of several immune cell types; however, the direct mechanism whereby they control natural killer (NK) cell function remains unclear. Three studies suggest Treg cells may attenuate NK cell activity by limiting the amount of interleukin-2 (IL-2) available.
In a mouse model of type 1 diabetes, Jonathan Sitrin et al. (J. Exp. Med. http://dx.doi.org/10.1084/jem.20122248) show that ablation of Treg cells induces the accumulation and activation of NK cells in the pancreas, leading to diabetes. Inhibition of IL-2, a cytokine previously shown to promote NK cell proliferation and interferon-γ (IFN-γ) production, reduced NK cell infiltration into the pancreas and their production of IFN-γ.
Georg Gasteiger et al. (J. Exp. Med. http://dx.doi.org/10.1084/jem.20122462; J. Exp. Med. http://dx.doi.org/10.1084/jem.20122571) report that Treg cell depletion induces systemic autoimmunity, leading to increased NK cell cytotoxicity toward missing self targets. This activity was dependent on IL-2, as inhibition of IL-2 or depletion of CD4+ cells, a dominant source of IL-2, reduced NK cell activity. Ablation of Treg cells also resulted in IL-2–dependent expansion of an immature subset of CD127+ NK cells. Taken together, these findings highlight how adaptive immune responses can control innate immune cell homeostasis and activation in the steady state and in disease.
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Da Silva, K. Restraining natural killer cells. Nat Med 19, 683 (2013). https://doi.org/10.1038/nm.3241
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DOI: https://doi.org/10.1038/nm.3241