Matthew J. Loza and Bice Perussia

IFN, produced during viral infections by accessory (type I IFN) or NK cells (type II IFN), play a primary role in the regulation of immune and anti-viral NK cell effector functions. Because IFN have anti-proliferative effects on several cell types, including hematopoietic cells, we asked whether they modulate proliferation of human NK cells, and whether IFN- and IFN- mediate distinct effects on NK cells at different developmental stages. Analysis of proliferation at the single-cell level in human NK cells indicated that both IFN types inhibit IL-4-induced accumulation of immature CD56– IL-13+ NK cells in freshly separated peripheral blood lymphocytes and in cells derived from them after short-term cultures. However, IFN- inhibited specifically the IL-4-dependent proliferation of these cells without affecting the IL-2-dependent one or that of the IL-13– cells, whereas IFN- attenuated proliferation of NK cells at any developmental stage (both immature CD56–IL-13+ and mature CD56+IL-13– IFN-+ NK cells) and contributed to their monokine-induced differentiation to IFN--producing cells. Adding to our previous report that IL-13 inhibits accumulation of mature IFN-+ NK cells, the present data unravel a mechanism by which peripheral immature IL-13+ and mature IFN-+ NK cells can negatively regulate each other’s accumulation.