Growth of murine natural killer cells from bone marrow in vitro: Role of TNFα and IFNγ

Abstract

It has been previously shown that natural killer (NK) cell growth can be induced by interleukin-2 (IL-2) in bone marrow (BM) cultures and that other cytokines (CKs), including IL-1α, act synergistically with IL-2. However, as the effect of IL-2 and IL-1α could be due to direct stimulation of NK progenitor cell growth, as well as to the induction of other factors, we analysed the role of the endogenous production of CKs in BM cultures. Results show that mRNAs specific for tumour necrosis factor-α (TNFα) and interferongamma (INFγ) are detectable within hours in BM cultures supplemented with IL-2 and IL-1α, and that the amount is higher when both IL-2 and IL-1α are present. Antibodies directed against TNFα and IFNγ abrogate the NK cell development, indicating that these CKs play an essential role. The antibodies, however, had no effect on mature NK cells. Furthermore, pretreatment of BM cells with TNFα or IFNγ before culturing with IL-2, enhances IL-2 responsiveness and NK cell growth. These results suggest that induction of cytokines production may be important for growth of NK cells from BM precursors and that the synergistic effect of IL-1α could be due, at least in part, to increased TNFα and IFNγ production.