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J Exp Med. Feb 1, 1988; 167(2): 452–472.
PMCID: PMC2188858

Interaction of Fc receptor (CD16) ligands induces transcription of interleukin 2 receptor (CD25) and lymphokine genes and expression of their products in human natural killer cells

Abstract

We report evidence that FcR(CD16) on human NK cells are signal- transducing molecules that, upon ligand binding, induce transcription of genes encoding surface activation molecules [IL-2-R(CD25)] and cytokines (IFN-gamma and TNF) relevant to NK cell biology and functions. Homogeneous NK and T cell populations purified from short- term bulk cultures of PBMC with irradiated B lymphoblastoid cell lines were cultured in the presence of FcR ligands (particulate immune complexes or immobilized anti-CD16 antibodies) alone or with rIL-2. Upon 18 h of stimulation, NK cells express Tac, TfR, and 4F2 antigens and produce IFN-gamma and TNF; both effects are synergistically enhanced in the presence of rIL-2, which is itself ineffective. Treatment of NK cells with FcR(CD16) ligands induces accumulation of mRNA for IFN-gamma and TNF and, to a lesser extent, IL-2-R with fast kinetics also in the absence of de novo protein synthesis. rIL-2 and FcR(CD16) ligands synergize to induce mRNA accumulation. mRNA accumulation and transcription of TNF and IFN-gamma genes induced by FcR(CD16) ligands are greater than those induced by rIL-2, and the reverse is true for IL-2-R. The two stimuli do not synergize at the transcriptional level. These observations indicate that the mechanisms through which FcR(CD16) ligands and rIL-2 induce NK cell activation are, in part, distinct. Both operate at the transcriptional level, although other mechanisms are probably induced by the FcR ligand stimulus per se or in combination with other lymphokines and synergize at a post-transcriptional or translational level to enhance NK cell activation.

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Selected References

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  • Perussia B, Trinchieri G. Antibody 3G8, specific for the human neutrophil Fc receptor, reacts with natural killer cells. J Immunol. 1984 Mar;132(3):1410–1415. [PubMed]
  • Fleit HB, Wright SD, Unkeless JC. Human neutrophil Fc gamma receptor distribution and structure. Proc Natl Acad Sci U S A. 1982 May;79(10):3275–3279. [PMC free article] [PubMed]
  • Unkeless JC. The presence of two Fc receptors on mouse macrophages: evidence from a variant cell line and differential trypsin sensitivity. J Exp Med. 1977 Apr 1;145(4):931–945. [PMC free article] [PubMed]
  • Perussia B, Trinchieri G, Jackson A, Warner NL, Faust J, Rumpold H, Kraft D, Lanier LL. The Fc receptor for IgG on human natural killer cells: phenotypic, functional, and comparative studies with monoclonal antibodies. J Immunol. 1984 Jul;133(1):180–189. [PubMed]
  • Ravetch JV, Luster AD, Weinshank R, Kochan J, Pavlovec A, Portnoy DA, Hulmes J, Pan YC, Unkeless JC. Structural heterogeneity and functional domains of murine immunoglobulin G Fc receptors. Science. 1986 Nov 7;234(4777):718–725. [PubMed]
  • Anderson CL, Guyre PM, Whitin JC, Ryan DH, Looney RJ, Fanger MW. Monoclonal antibodies to Fc receptors for IgG on human mononuclear phagocytes. Antibody characterization and induction of superoxide production in a monocyte cell line. J Biol Chem. 1986 Sep 25;261(27):12856–12864. [PubMed]
  • Vaughn M, Taylor M, Mohanakumar T. Characterization of human IgG Fc receptors. J Immunol. 1985 Dec;135(6):4059–4065. [PubMed]
  • Perussia B, Acuto O, Terhorst C, Faust J, Lazarus R, Fanning V, Trinchieri G. Human natural killer cells analyzed by B73.1, a monoclonal antibody blocking Fc receptor functions. II. Studies of B73.1 antibody-antigen interaction on the lymphocyte membrane. J Immunol. 1983 May;130(5):2142–2148. [PubMed]
  • Perussia B, Trinchieri G, Cerottini JC. Functional studies of Fc receptor-bearing human lymphocytes: effect of treatment with proteolytic enzymes. J Immunol. 1979 Aug;123(2):681–687. [PubMed]
  • Jondal M, Kullman C, Alter MB, Ljunggren K. Monoclonal antibodies against the NK cell-FcR and the T3-complex potentiate normal lymphocyte killing. Cell Immunol. 1986 Jun;100(1):158–166. [PubMed]
  • Ledbetter JA, June CH, Martin PJ, Spooner CE, Hansen JA, Meier KE. Valency of CD3 binding and internalization of the CD3 cell-surface complex control T cell responses to second signals: distinction between effects on protein kinase C, cytoplasmic free calcium, and proliferation. J Immunol. 1986 Jun 1;136(11):3945–3952. [PubMed]
  • Meuer SC, Hussey RE, Cantrell DA, Hodgdon JC, Schlossman SF, Smith KA, Reinherz EL. Triggering of the T3-Ti antigen-receptor complex results in clonal T-cell proliferation through an interleukin 2-dependent autocrine pathway. Proc Natl Acad Sci U S A. 1984 Mar;81(5):1509–1513. [PMC free article] [PubMed]
  • Scheurich P, Ucer U, Wrann M, Pfizenmaier K. Early events during primary activation of T cells: antigen receptor cross-linking and interleukin 1 initiate proliferative response of human T cells. Eur J Immunol. 1985 Nov;15(11):1091–1095. [PubMed]
  • Kammer GM, Kurrasch R, Scillian JJ. Capping of the surface OKT3 binding molecule prevents the T-cell proliferative response to antigens: evidence that this molecule conveys the activation signal. Cell Immunol. 1984 Aug;87(1):284–294. [PubMed]
  • Pantaleo G, Olive D, Poggi A, Pozzan T, Moretta L, Moretta A. Antibody-induced modulation of the CD3/T cell receptor complex causes T cell refractoriness by inhibiting the early metabolic steps involved in T cell activation. J Exp Med. 1987 Aug 1;166(2):619–624. [PMC free article] [PubMed]
  • Weiss A, Imboden J, Wiskocil R, Stobo J. The role of T3 in the activation of human T cells. J Clin Immunol. 1984 May;4(3):165–173. [PubMed]
  • Tsudo M, Goldman CK, Bongiovanni KF, Chan WC, Winton EF, Yagita M, Grimm EA, Waldmann TA. The p75 peptide is the receptor for interleukin 2 expressed on large granular lymphocytes and is responsible for the interleukin 2 activation of these cells. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5394–5398. [PMC free article] [PubMed]
  • Trinchieri G, Matsumoto-Kobayashi M, Clark SC, Seehra J, London L, Perussia B. Response of resting human peripheral blood natural killer cells to interleukin 2. J Exp Med. 1984 Oct 1;160(4):1147–1169. [PMC free article] [PubMed]
  • Phillips JH, Le AM, Lanier LL. Natural killer cells activated in a human mixed lymphocyte response culture identified by expression of Leu-11 and class II histocompatibility antigens. J Exp Med. 1984 Apr 1;159(4):993–1008. [PMC free article] [PubMed]
  • London L, Perussia B, Trinchieri G. Induction of proliferation in vitro of resting human natural killer cells: IL 2 induces into cell cycle most peripheral blood NK cells, but only a minor subset of low density T cells. J Immunol. 1986 Dec 15;137(12):3845–3854. [PubMed]
  • Wright SC, Bonavida B. Studies on the mechanism of natural killer (NK) cell-mediated cytotoxicity (CMC). I. Release of cytotoxic factors specific for NK-sensitive target cells (NKCF) during co-culture of NK effector cells with NK target cells. J Immunol. 1982 Jul;129(1):433–439. [PubMed]
  • Degliantoni G, Murphy M, Kobayashi M, Francis MK, Perussia B, Trinchieri G. Natural killer (NK) cell-derived hematopoietic colony-inhibiting activity and NK cytotoxic factor. Relationship with tumor necrosis factor and synergism with immune interferon. J Exp Med. 1985 Nov 1;162(5):1512–1530. [PMC free article] [PubMed]
  • Liu CC, Perussia B, Cohn ZA, Young JD. Identification and characterization of a pore-forming protein of human peripheral blood natural killer cells. J Exp Med. 1986 Dec 1;164(6):2061–2076. [PMC free article] [PubMed]
  • Perussia B, Ramoni C, Anegon I, Cuturi MC, Faust J, Trinchieri G. Preferential proliferation of natural killer cells among peripheral blood mononuclear cells cocultured with B lymphoblastoid cell lines. Nat Immun Cell Growth Regul. 1987;6(4):171–188. [PubMed]
  • Perussia B, Starr S, Abraham S, Fanning V, Trinchieri G. Human natural killer cells analyzed by B73.1, a monoclonal antibody blocking Fc receptor functions. I. Characterization of the lymphocyte subset reactive with B73.1. J Immunol. 1983 May;130(5):2133–2141. [PubMed]
  • Perussia B, Trinchieri G, Lebman D, Jankiewicz J, Lange B, Rovera G. Monoclonal antibodies that detect differentiation surface antigens on human myelomonocytic cells. Blood. 1982 Feb;59(2):382–392. [PubMed]
  • Perussia B, Lebman D, Ip SH, Rovera G, Trinchieri G. Terminal differentiation surface antigens of myelomonocytic cells are expressed in human promyelocytic leukemia cells (HL60) treated with chemical inducers. Blood. 1981 Oct;58(4):836–843. [PubMed]
  • Griffin JD, Hercend T, Beveridge R, Schlossman SF. Characterization of an antigen expressed by human natural killer cells. J Immunol. 1983 Jun;130(6):2947–2951. [PubMed]
  • Cuturi MC, Murphy M, Costa-Giomi MP, Weinmann R, Perussia B, Trinchieri G. Independent regulation of tumor necrosis factor and lymphotoxin production by human peripheral blood lymphocytes. J Exp Med. 1987 Jun 1;165(6):1581–1594. [PMC free article] [PubMed]
  • Lanier LL, Le AM, Civin CI, Loken MR, Phillips JH. The relationship of CD16 (Leu-11) and Leu-19 (NKH-1) antigen expression on human peripheral blood NK cells and cytotoxic T lymphocytes. J Immunol. 1986 Jun 15;136(12):4480–4486. [PubMed]
  • Murphy M, Loudon R, Kobayashi M, Trinchieri G. Gamma interferon and lymphotoxin, released by activated T cells, synergize to inhibit granulocyte/monocyte colony formation. J Exp Med. 1986 Jul 1;164(1):263–279. [PMC free article] [PubMed]
  • Krönke M, Leonard WJ, Depper JM, Arya SK, Wong-Staal F, Gallo RC, Waldmann TA, Greene WC. Cyclosporin A inhibits T-cell growth factor gene expression at the level of mRNA transcription. Proc Natl Acad Sci U S A. 1984 Aug;81(16):5214–5218. [PMC free article] [PubMed]
  • Groudine M, Peretz M, Weintraub H. Transcriptional regulation of hemoglobin switching in chicken embryos. Mol Cell Biol. 1981 Mar;1(3):281–288. [PMC free article] [PubMed]
  • Gariglio P, Bellard M, Chambon P. Clustering of RNA polymerase B molecules in the 5' moiety of the adult beta-globin gene of hen erythrocytes. Nucleic Acids Res. 1981 Jun 11;9(11):2589–2598. [PMC free article] [PubMed]
  • Yamada S, Ruscetti FW, Overton WR, Herberman RB, Birchenall-Sparks MC, Ortaldo JR. Regulation of human large granular lymphocyte and T cell growth and function by recombinant interleukin 2: induction of interleukin 2 receptor and promotion of growth of cells with enhanced cytotoxicity. J Leukoc Biol. 1987 Jun;41(6):505–517. [PubMed]
  • Young HA, Ortaldo JR. One-signal requirement for interferon-gamma production by human large granular lymphocytes. J Immunol. 1987 Aug 1;139(3):724–727. [PubMed]
  • Le J, Yao JS, Knowles DM, 2nd, Vilcek J. Accessory function of thymic and tonsillar dendritic cells in interferon gamma production by T lymphocytes. Lymphokine Res. 1986 Summer;5(3):205–213. [PubMed]
  • Perussia B, Trinchieri G. Inactivation of natural killer cell cytotoxic activity after interaction with target cells. J Immunol. 1981 Feb;126(2):754–758. [PubMed]
  • Lanier LL, Kipps TJ, Phillips JH. Functional properties of a unique subset of cytotoxic CD3+ T lymphocytes that express Fc receptors for IgG (CD16/Leu-11 antigen). J Exp Med. 1985 Dec 1;162(6):2089–2106. [PMC free article] [PubMed]
  • Ostensen ME, Thiele DL, Lipsky PE. Tumor necrosis factor-alpha enhances cytolytic activity of human natural killer cells. J Immunol. 1987 Jun 15;138(12):4185–4191. [PubMed]
  • Scheurich P, Thoma B, Ucer U, Pfizenmaier K. Immunoregulatory activity of recombinant human tumor necrosis factor (TNF)-alpha: induction of TNF receptors on human T cells and TNF-alpha-mediated enhancement of T cell responses. J Immunol. 1987 Mar 15;138(6):1786–1790. [PubMed]
  • Miller LJ, Bainton DF, Borregaard N, Springer TA. Stimulated mobilization of monocyte Mac-1 and p150,95 adhesion proteins from an intracellular vesicular compartment to the cell surface. J Clin Invest. 1987 Aug;80(2):535–544. [PMC free article] [PubMed]
  • Metzger H, Alcaraz G, Hohman R, Kinet JP, Pribluda V, Quarto R. The receptor with high affinity for immunoglobulin E. Annu Rev Immunol. 1986;4:419–470. [PubMed]
  • Olabuenaga SE, Brooks CG, Gillis S, Henney CS. Interleukin 2 is not sufficient for the continuous growth of cloned NK-like cytotoxic cell lines. J Immunol. 1983 Nov;131(5):2386–2391. [PubMed]
  • Lebendiker MA, Tal C, Sayar D, Pilo S, Eilon A, Banai Y, Kaempfer R. Superinduction of the human gene encoding immune interferon. EMBO J. 1987 Mar;6(3):585–589. [PMC free article] [PubMed]
  • Collart MA, Belin D, Vassalli JD, de Kossodo S, Vassalli P. Gamma interferon enhances macrophage transcription of the tumor necrosis factor/cachectin, interleukin 1, and urokinase genes, which are controlled by short-lived repressors. J Exp Med. 1986 Dec 1;164(6):2113–2118. [PMC free article] [PubMed]

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