NATURAL-KILLER (NK) CELL GENERATION IN BONE-MARROW CULTURES - ROLE OF IL-1-ALPHA

Previous studies have demonstrated that IL-2 is able to induce the development of NK cells from bone marrow (BM) cultures, and that other cytokines acted synergistically with IL-2 in determining an increase of NK cells development. The addition of TNF-alpha greatly enhanced the IL-2-mediated induction of NK effector. However, the effect of IL-2 and TNF-alpha could be due to direct stimulation of NK progenitors, or to the endogenous production of other factors, which are then responsible of the development of NK cells. As results show that the mRNA specific for IL-1-alpha could be detected in BM cells cultured with IL-2, but not in that supplemented with IL-2 + TNF-alpha, it would seem that this lymphokine plays a role only in IL-2-dependent development of NK cells. Studies with Ab anti- IL-1-alpha, showed that the antibody abrograted the IL-2-driven generation of NK cells, but did not affect the NK differentiation induced by IL-2 + TNF-alpha. The cytotoxic cells generated by IL-2 or by IL-2 + TNF-alpha had the phenotype of mature NK cells including expression of NK 1.1, asialo GM1, Lyt-5, LFA-1, and Thy-1. These data suggest that in spite of phenotypical and morphological similarity of the cells generated with IL-2 or IL-2 + TNF-alpha, the endogenous production of IL-1-alpha, appears functionally improtant only for the differentiation of NK cells induced by IL-2 alone.