A critical role for IL-18 in the proliferation and activation of NK1.1(+)CD3(-) cells

作者：Tomura M; Zhou XY; Maruo S; Ahn HJ; Hamaoka T; Okamura H; Nakanishi K; Tanimoto T; Kurimoto M; Fujiwara H^*

来源：The Journal of Immunology, 1998, 160(10): 4738-4746.

Like IL-12, IFN-gamma-inducing factor/IL-18 has been shown to stimulate T cells for IFN-gamma production and growth promotion. Considering the NK-stimulatory capacity of IL-12, we investigated the effect of IL-18 on NK lineage cells. A CD4(-)CD8(-) surface Ig(-)Ia(-) fraction of freshly prepared C57BL/6 spleen cells proliferated strikingly in response to combinations of IL-12 + IL-18 or IL-2 + IL-18, but not to the individual cytokines or IL-2 + IL-12, Cells proliferating in response to IL-2 + IL-18 were NK1.1(+)CD3(-), whereas IL-12 + IL-18-responsive cells were NK1.1(-)CD3(-). Restimulation of the former cells with IL-12 + IL-18 or the latter cells with IL-2 + IL-18 resulted in the generation of NK1.1(-)CD3(-) or NK1.1(+)CD3(-) cells, respectively. Moreover, a NK1.1(-)CD3(-)CD4(-)CD8(-) surface Ig(-)Ia(-) population isolated from spleen cells was found to form NK1.1(+)CD3(-) or NK1.1(-)CD3(-) blasts by stimulation with IL-2 + IL-18 or IL-12 + IL-18, respectively, and the NK1.1 positivity on these blasts was again reversed after restimulation with an alternative combined stimulus. Both types of blasts produced enormously large amounts of IFN-gamma in response to IL-12 + IL-18 and exhibited strikingly high levels of NK activity. These results indicate that IL-18 plays an obligatory role in inducing proliferation and activation of NK1.1(+)CD3(-)CD4(-)CD8(-) cells and that the expression of the NK1.1 marker is reversible, depending on the cytokine used for stimulation in combination with IL-18.

• 出版日期1998-5-15