GROWTH OF MURINE NATURAL-KILLER-CELLS FROM BONE-MARROW INVITRO - ROLE OF TNF-ALPHA AND IFN-GAMMA

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-1-alpha, act synergistically with IL-2. However, as the effect of IL-2 and IL-1-alpha 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-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) are detectable within hours in BM cultures supplemented with IL-2 and IL-1-alpha, and that the amount is higher when both IL-2 and IL-1-alpha are present. Antibodies directed against TNF-alpha and IFN-gamma 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 TNF-alpha or IFN-gamma 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-1-alpha could be due, at least in part, to increased TNF-alpha and IFN-gamma production.