Development and function of IL-10 IFN-gamma-secreting CD4(+) T cells.

IL-10 IFN-gamma-secreting CD4(+) T cells were first found in the early 1990s. They are suppressive T cells able to inhibit cytotoxic T lymphocytes. These cells (Foxp3-T bet(+)) have a similar function but are distinct from conventional Tregs. The production of IL-10 in these cells requires IL-27 and TGF-beta and was regulated by several signal pathways including Notch, STAT, and NF-kappaB. The crosstalk among these pathways is critical for the generation and function of these cells. IL-10 IFN-gamma-secreting CD4(+) T cells are activated in chronic infection and are responsible for prolonged infection. Thus, their modulation has therapeutic implications for the treatment of infectious diseases. However, it is complicated, and fine-tuning of IFN-gamma and IL-10 secretion by these cells is needed for disease management, as inhibition of these cells will also lead to overimmune responses. On the other hand, increasing their numbers in autoimmune diseases may have beneficial effects.