Regulation of NK cells through the 80-kDa TNFR (CD120b).

By using monoclonal antibody specific for tumor necrosis factor receptor80 (TNFR80) (CD120b) and TNFR60 (CD120a), we determined which receptor transduces the signals involved in activating natural killer (NK) cells. Purified CD56+CD3- large lymphocytes express TNFR80 but not TNFR60 and interleukin-2 (IL-2) up-regulates TNFR80 expression, consistent with NK cells being activated in vivo. Treatment of NK cells with anti-TNFR80 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-TNFR80 abrogated IL-2 induction of lymphokine-activated killer cell activity. The activity of TNF or anti-TNFR80 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 TNFR80 is an important signal transducing receptor for the differentiation of NK cells induced by TNF and IL-2.