REGULATION OF NK CELLS THROUGH THE 80-KDA TNFR (CD120B)

By using monoclonal antibody specific for tumor necrosis factor receptor(80) (TNFR(80)) (CD120b) and TNFR(60) (CD120a), we determined which receptor transduces the signals involved in activating natural killer (NK) cells, Purified CD56(+)CD3(-) large lymphocytes express TNFR(80) but not TNFR(80) and interleukin-2 (IL-2) up-regulates TNFR(80) expression, consistent with NK cells being activated in vivo, Treatment of NK cells with anti-TNFR(80) for 18 h enhanced the NK activity detected on K562 target cells mimicking the effect of TNF, In combination with IL-2, TNF enhanced the development of lymphokine-activated killing. However, only anti-TNFR(80) abrogated IL-2 induction of lymphokine-activated killer cell activity, The activity of TNF or anti-TNFR(80) was selective for NK cytotoxic function because they did not directly mimic IL-2 activation or induce significant proliferation, expression of cell surface activation antigens (CD25 or HLA-DR), or interferon-gamma secretion, These results indicate that TNFR(80) is an important signal transducing receptor for the differentiation of NK cells induced by TNF and IL-2.