Mason A T, McVicar D W, Smith C A, Young H A, Ware C F, Ortaldo J R
Laboratory of Experimental Immunology, NCI-FCRDC, Frederick, Maryland 21702-1201, USA.
J Leukoc Biol. 1995 Aug;58(2):249-55. doi: 10.1002/jlb.58.2.249.
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.
