title: Differential effects of tyrosine kinase inhibition in CD69 antigen expression and lytic activity induced by rIL-2, rIL-12, and rIFN-alpha in human NK cells.
abstract: The effect of rIL-12 on induction of CD69 antigen expression and cytolytic activity in purified human NK cells was evaluated in comparison to the effects of rIL-2 and rIFN-alpha. It was found that rIL-12 directly induced CD69 antigen expression in NK cells, although the period of incubation required by rIL-12 was longer than the period required by rIL-2 or by rIFN-alpha. Similarly, the cytolytic activity induced by rIL-12 in NK cells against the NK-resistant target cell line Raji was consistently lower than the cytolytic activity induced by rIL-2 or rIFN-alpha when measured after 6 hr of incubation, and increased during the following 18 hr of incubation. To compare the involvement of tyrosin kinases in activation of NK cells induced by rIL-2, rIL-12, and rIFN-alpha, the effect of the specific inhibitor of tyrosin kinases, genistein, was evaluated on induction of CD69 antigen expression and lytic function mediated by the three cytokines. It was found that genistein inhibited CD69 antigen expression induced by rIL-2 and by rIL-12, but not that induced by rIFN-alpha. Unlike the effect on CD69 antigen expression, the cytolytic activity induced by all three cytokines was inhibited by genistein. These results, together with the finding that CD69 antigen expression induced by rIL-2 but not by rIL-12 or rIFN-alpha was inhibited by addition of rIL-4, strongly suggest that IL-2, IL-12, and IFN-alpha mediate their effects, leading to induction of CD69 antigen expression through different activation pathways.
authors.affiliation: Istituto di Immunologia e Malattie Infettive, Policlinico di Borgo Roma, Verona, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Gerosa
authors.forename: M
authors.initials: M
authors.lastname: Tommasi
authors.forename: C
authors.initials: C
authors.lastname: Benati
authors.forename: G
authors.initials: G
authors.lastname: Gandini
authors.forename: M
authors.initials: M
authors.lastname: Libonati
authors.forename: G
authors.initials: G
authors.lastname: Tridente
authors.forename: G
authors.initials: G
authors.lastname: Carra
authors.forename: G
authors.initials: G
authors.lastname: Trinchieri
mesh_terms: D015703:Antigens, CD / Q000032:analysis*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D019833:Genistein; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D018664:Interleukin-12; D007376:Interleukin-2 / Q000494:pharmacology*; D007378:Interleukins / Q000494:pharmacology*; D007529:Isoflavones / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D037181:Lectins, C-Type; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins / Q000494:pharmacology; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D019833:Genistein; D016898:Interferon-alpha; D018664:Interleukin-12; D007376:Interleukin-2; D007378:Interleukins; D007529:Isoflavones; D037181:Lectins, C-Type; D011505:Protein-Tyrosine Kinases; D011994:Recombinant Proteins; D000099192:CD69 Antigens