title: Regulation of NK cells through the 80-kDa TNFR (CD120b).
abstract: 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.
authors.affiliation: Laboratory of Experimental Immunology, NCI-FCRDC, Frederick, Maryland 21702-1201, USA.
authors.forename: A T
authors.initials: AT
authors.lastname: Mason
authors.forename: D W
authors.initials: DW
authors.lastname: McVicar
authors.forename: C A
authors.initials: CA
authors.lastname: Smith
authors.forename: H A
authors.initials: HA
authors.lastname: Young
authors.forename: C F
authors.initials: CF
authors.lastname: Ware
authors.forename: J R
authors.initials: JR
authors.lastname: Ortaldo
mesh_terms: D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects / Q000276:immunology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology*; D010750:Phosphoproteins / Q000096:biosynthesis / Q000302:isolation & purification; D019000:Phosphotyrosine; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D047889:Receptors, Tumor Necrosis Factor, Type II; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D007376:Interleukin-2; D010750:Phosphoproteins; D018124:Receptors, Tumor Necrosis Factor; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D019000:Phosphotyrosine; D014443:Tyrosine; D007371:Interferon-gamma