Interactions between NK cells and regulatory T cells

Regulatory T cells (Treg) maintain peripheral tolerance and prevent the development of autoimmune diseases. They control the function of different immune cells such as differentiated CD4⁺ and CD8⁺ T cells, B cells, and dendritic cells. We and others contributed to demonstrate that Treg also regulate NK cell functions in mice and humans. Treg hamper the homeostatic proliferation of NK cells, NKG2D-dependent NK cell cytotoxic activity, and IL-12-induced NK cell IFNγ secretion. In vivo, in the absence of Tregs, NK cell proliferation ensures in lymph nodes through an autoreactive crosstalk between resident dendritic cells (DC) and CD4⁺ T lymphocytes leading to IL-15Rα exposure on DC. During tumor progression, Treg play a dominant role in suppressing the innate arm of antitumor immune responses. We will discuss strategies currently developed to impede Treg inhibitory effects in cancer.