J. Exp. Med., Volume 188, Number 12, December 21, 1998 2375-2380

Natural Killer (NK) Cell-mediated Cytotoxicity: Differential Use of  TRAIL and Fas Ligand by Immature and Mature Primary Human NK Cells

By Loris Zamai, Manzoor Ahmad, Ian M. Bennett, Livio Azzoni, Emad S. Alnemri, and Bice Perussia

From the Jefferson Medical College, Department of Microbiology and Immunology, Kimmel Cancer Institute, Philadelphia, Pennsylvania 19107

Mature natural killer (NK) cells use Ca²⁺-dependent granule exocytosis and release of cytotoxic proteins, Fas ligand (FasL), and membrane-bound or secreted cytokines (tumor necrosis factor [TNF]-) to induce target cell death. Fas belongs to the TNF receptor family of molecules, containing a conserved intracytoplasmic "death domain" that indirectly activates the caspase enzymatic cascade and ultimately apoptotic mechanisms in numerous cell types. Two additional members of this family, DR4 and DR5, transduce apoptotic signals upon binding soluble TNF-related apoptosis-inducing ligand (TRAIL) that, like FasL, belongs to the growing TNF family of molecules. Here, we report that TRAIL produced or expressed by different populations of primary human NK cells is functional, and represents a marker of differentiation or activation of these, and possibly other, cytotoxic leukocytes. During differentiation NK cells, sequentially and differentially, use distinct members of the TNF family or granule exocytosis to mediate target cell death. Phenotypically immature CD161⁺/CD56 NK cells mediate TRAIL-dependent but not FasL- or granule release-dependent cytotoxicity, whereas mature CD56⁺ NK cells mediate the latter two.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Haraguchi, K., Suzuki, T., Koyama, N., Kumano, K., Nakahara, F., Matsumoto, A., Yokoyama, Y., Sakata-Yanagimoto, M., Masuda, S., Takahashi, T., Kamijo, A., Takahashi, K., Takanashi, M., Okuyama, Y., Yasutomo, K., Sakano, S., Yagita, H., Kurokawa, M., Ogawa, S., Chiba, S. (2009). Notch Activation Induces the Generation of Functional NK Cells from Human Cord Blood CD34-Positive Cells Devoid of IL-15. J. Immunol. 182: 6168-6178 [Abstract] [Full Text]  
• Zebedin, E., Simma, O., Schuster, C., Putz, E. M., Fajmann, S., Warsch, W., Eckelhart, E., Stoiber, D., Weisz, E., Schmid, J. A., Pickl, W. F., Baumgartner, C., Valent, P., Piekorz, R. P., Freissmuth, M., Sexl, V. (2008). Leukemic challenge unmasks a requirement for PI3K{delta} in NK cell-mediated tumor surveillance. Blood 112: 4655-4664 [Abstract] [Full Text]  
• Iannello, A., Debbeche, O., Samarani, S., Ahmad, A. (2008). Antiviral NK cell responses in HIV infection: I. NK cell receptor genes as determinants of HIV resistance and progression to AIDS. J. Leukoc. Biol. 84: 1-26 [Abstract] [Full Text]  
• Silva, A., Andrews, D. M., Brooks, A. G., Smyth, M. J., Hayakawa, Y. (2008). Application of CD27 as a marker for distinguishing human NK cell subsets. Int Immunol 20: 625-630 [Abstract] [Full Text]  
• Simons, M. P., Leidal, K. G., Nauseef, W. M., Griffith, T. S. (2008). TNF-related apoptosis-inducing ligand (TRAIL) is expressed throughout myeloid development, resulting in a broad distribution among neutrophil granules. J. Leukoc. Biol. 83: 621-629 [Abstract] [Full Text]  
• Papewalis, C., Jacobs, B., Wuttke, M., Ullrich, E., Baehring, T., Fenk, R., Willenberg, H. S., Schinner, S., Cohnen, M., Seissler, J., Zacharowski, K., Scherbaum, W. A., Schott, M. (2008). IFN-{alpha} Skews Monocytes into CD56+-Expressing Dendritic Cells with Potent Functional Activities In Vitro and In Vivo. J. Immunol. 180: 1462-1470 [Abstract] [Full Text]  
• Zamai, L., Ponti, C., Mirandola, P., Gobbi, G., Papa, S., Galeotti, L., Cocco, L., Vitale, M. (2007). NK Cells and Cancer. J. Immunol. 178: 4011-4016 [Abstract] [Full Text]  
• Johansson, M. H., Taylor, M. A., Jagodic, M., Tus, K., Schatzle, J. D., Wakeland, E. K., Bennett, M. (2006). Mapping of Quantitative Trait Loci Determining NK Cell-Mediated Resistance to MHC Class I-Deficient Bone Marrow Grafts in Perforin-Deficient Mice. J. Immunol. 177: 7923-7929 [Abstract] [Full Text]  
• Marcenaro, S., Gallo, F., Martini, S., Santoro, A., Griffiths, G. M., Arico, M., Moretta, L., Pende, D. (2006). Analysis of natural killer-cell function in familial hemophagocytic lymphohistiocytosis (FHL): defective CD107a surface expression heralds Munc13-4 defect and discriminates between genetic subtypes of the disease. Blood 108: 2316-2323 [Abstract] [Full Text]  
• Song, K., Benhaga, N., Anderson, R. L., Khosravi-Far, R. (2006). Transduction of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand into Hematopoietic Cells Leads to Inhibition of Syngeneic Tumor Growth In vivo.. Cancer Res. 66: 6304-6311 [Abstract] [Full Text]  
• Hsiao, H.-L., Wang, W.-S., Chen, P.-M., Su, Y. (2006). Overexpression of thymosin {beta}-4 renders SW480 colon carcinoma cells more resistant to apoptosis triggered by FasL and two topoisomerase II inhibitors via downregulating Fas and upregulating Survivin expression, respectively. Carcinogenesis 27: 936-944 [Abstract] [Full Text]  
• Freud, A. G., Yokohama, A., Becknell, B., Lee, M. T., Mao, H. C., Ferketich, A. K., Caligiuri, M. A. (2006). Evidence for discrete stages of human natural killer cell differentiation in vivo. JEM 203: 1033-1043 [Abstract] [Full Text]  
• Huang, C., Bi, E., Hu, Y., Deng, W., Tian, Z., Dong, C., Hu, Y., Sun, B. (2006). A Novel NF-{kappa}B Binding Site Controls Human Granzyme B Gene Transcription. J. Immunol. 176: 4173-4181 [Abstract] [Full Text]  
• Cassatella, M. A., Huber, V., Calzetti, F., Margotto, D., Tamassia, N., Peri, G., Mantovani, A., Rivoltini, L., Tecchio, C. (2006). Interferon-activated neutrophils store a TNF-related apoptosis-inducing ligand (TRAIL/Apo-2 ligand) intracellular pool that is readily mobilizable following exposure to proinflammatory mediators. J. Leukoc. Biol. 79: 123-132 [Abstract] [Full Text]  
• Mundt, B, Wirth, T, Zender, L, Waltemathe, M, Trautwein, C, Manns, M P, Kuhnel, F, Kubicka, S (2005). Tumour necrosis factor related apoptosis inducing ligand (TRAIL) induces hepatic steatosis in viral hepatitis and after alcohol intake. Gut 54: 1590-1596 [Abstract] [Full Text]  
• Sandra, F., Degli Esposti, M., Ndebele, K., Gona, P., Knight, D., Rosenquist, M., Khosravi-Far, R. (2005). Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Alters Mitochondrial Membrane Lipids. Cancer Res. 65: 8286-8297 [Abstract] [Full Text]  
• Bruning, A., Stickeler, E., Diederich, D., Walz, L., Rohleder, H., Friese, K., Runnebaum, I. B. (2005). Coxsackie and Adenovirus Receptor Promotes Adenocarcinoma Cell Survival and Is Expressionally Activated after Transition from Preneoplastic Precursor Lesions to Invasive Adenocarcinomas. Clin. Cancer Res. 11: 4316-4320 [Abstract] [Full Text]  
• Nguyen, S., Dhedin, N., Vernant, J.-P., Kuentz, M., Jijakli, A. A., Rouas-Freiss, N., Carosella, E. D., Boudifa, A., Debre, P., Vieillard, V. (2005). NK-cell reconstitution after haploidentical hematopoietic stem-cell transplantations: immaturity of NK cells and inhibitory effect of NKG2A override GvL effect. Blood 105: 4135-4142 [Abstract] [Full Text]  
• Takeda, K., Cretney, E., Hayakawa, Y., Ota, T., Akiba, H., Ogasawara, K., Yagita, H., Kinoshita, K., Okumura, K., Smyth, M. J. (2005). TRAIL identifies immature natural killer cells in newborn mice and adult mouse liver. Blood 105: 2082-2089 [Abstract] [Full Text]  
• Jin, T.-G., Kurakin, A., Benhaga, N., Abe, K., Mohseni, M., Sandra, F., Song, K., Kay, B. K., Khosravi-Far, R. (2004). Fas-associated Protein with Death Domain (FADD)-independent Recruitment of c-FLIPL to Death Receptor 5. J. Biol. Chem. 279: 55594-55601 [Abstract] [Full Text]  
• He, Y.-G., Mayhew, E., Mellon, J., Niederkorn, J. Y. (2004). Expression and Possible Function of IL-2 and IL-15 Receptors on Human Uveal Melanoma Cells. IOVS 45: 4240-4246 [Abstract] [Full Text]  
• Li, S., Xu, J., Makarenkova, V. P., Tjandrawan, T., Vakkila, J., Reichert, T., Gooding, W., Lagenaur, C. F., Achim, C. L., Chambers, W. H., Herberman, R. B., Whiteside, T. L., Vujanovic, N. L. (2004). A novel epitope of N-CAM defines precursors of human adherent NK cells. J. Leukoc. Biol. 76: 1187-1199 [Abstract] [Full Text]  
• Mirandola, P., Ponti, C., Gobbi, G., Sponzilli, I., Vaccarezza, M., Cocco, L., Zauli, G., Secchiero, P., Manzoli, F. A., Vitale, M. (2004). Activated human NK and CD8+ T cells express both TNF-related apoptosis-inducing ligand (TRAIL) and TRAIL receptors but are resistant to TRAIL-mediated cytotoxicity. Blood 104: 2418-2424 [Abstract] [Full Text]  
• Ahmad, A., Alvarez, F. (2004). Role of NK and NKT cells in the immunopathogenesis of HCV-induced hepatitis. J. Leukoc. Biol. 76: 743-759 [Abstract] [Full Text]  
• Lum, J. J., Schnepple, D. J., Nie, Z., Sanchez-Dardon, J., Mbisa, G. L., Mihowich, J., Hawley, N., Narayan, S., Kim, J. E., Lynch, D. H., Badley, A. D. (2004). Differential Effects of Interleukin-7 and Interleukin-15 on NK Cell Anti-Human Immunodeficiency Virus Activity. J. Virol. 78: 6033-6042 [Abstract] [Full Text]  
• Tecchio, C., Huber, V., Scapini, P., Calzetti, F., Margotto, D., Todeschini, G., Pilla, L., Martinelli, G., Pizzolo, G., Rivoltini, L., Cassatella, M. A. (2004). IFN{alpha}-stimulated neutrophils and monocytes release a soluble form of TNF-related apoptosis-inducing ligand (TRAIL/Apo-2 ligand) displaying apoptotic activity on leukemic cells. Blood 103: 3837-3844 [Abstract] [Full Text]  
• Loza, M. J., Perussia, B. (2004). The IL-12 Signature: NK Cell Terminal CD56+high Stage and Effector Functions. J. Immunol. 172: 88-96 [Abstract] [Full Text]  
• Hayakawa, Y., Screpanti, V., Yagita, H., Grandien, A., Ljunggren, H.-G., Smyth, M. J., Chambers, B. J. (2004). NK Cell TRAIL Eliminates Immature Dendritic Cells In Vivo and Limits Dendritic Cell Vaccination Efficacy. J. Immunol. 172: 123-129 [Abstract] [Full Text]  
• Koh, C. Y., Ortaldo, J. R., Blazar, B. R., Bennett, M., Murphy, W. J. (2003). NK-cell purging of leukemia: superior antitumor effects of NK cells H2 allogeneic to the tumor and augmentation with inhibitory receptor blockade. Blood 102: 4067-4075 [Abstract] [Full Text]  
• Schott, E., Bonasio, R., Ploegh, H. L. (2003). Elimination In Vivo of Developing T Cells by Natural Killer Cells. JEM 198: 1213-1224 [Abstract] [Full Text]  
• Lamhamedi-Cherradi, S.-E., Zheng, S., Tisch, R. M., Chen, Y. H. (2003). Critical Roles of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand in Type 1 Diabetes. Diabetes 52: 2274-2278 [Abstract] [Full Text]  
• Obata-Onai, A., Hashimoto, S.-i., Onai, N., Kurachi, M., Nagai, S., Shizuno, K.-i., Nagahata, T., Matsushima, K. (2002). Comprehensive gene expression analysis of human NK cells and CD8+ T lymphocytes. Int Immunol 14: 1085-1098 [Abstract] [Full Text]  
• Secchiero, P., Gonelli, A., Mirandola, P., Melloni, E., Zamai, L., Celeghini, C., Milani, D., Zauli, G. (2002). Tumor necrosis factor-related apoptosis-inducing ligand induces monocytic maturation of leukemic and normal myeloid precursors through a caspase-dependent pathway. Blood 100: 2421-2429 [Abstract] [Full Text]  
• Azzoni, L., Papasavvas, E., Chehimi, J., Kostman, J. R., Mounzer, K., Ondercin, J., Perussia, B., Montaner, L. J. (2002). Sustained Impairment of IFN-{gamma} Secretion in Suppressed HIV-Infected Patients Despite Mature NK Cell Recovery: Evidence for a Defective Reconstitution of Innate Immunity. J. Immunol. 168: 5764-5770 [Abstract] [Full Text]  
• Zhang, H.-G., Xie, J., Xu, L., Yang, P., Xu, X., Sun, S., Wang, Y., Curiel, D. T., Hsu, H.-C., Mountz, J. D. (2002). Hepatic DR5 Induces Apoptosis and Limits Adenovirus Gene Therapy Product Expression in the Liver. J. Virol. 76: 5692-5700 [Abstract] [Full Text]  
• Chu, P., Deforce, D., Pedersen, I. M., Kim, Y., Kitada, S., Reed, J. C., Kipps, T. J. (2002). Latent sensitivity to Fas-mediated apoptosis after CD40 ligation may explain activity of CD154 gene therapy in chronic lymphocytic leukemia. Proc. Natl. Acad. Sci. USA 99: 3854-3859 [Abstract] [Full Text]  
• Lu, G., Janjic, B. M., Janjic, J., Whiteside, T. L., Storkus, W. J., Vujanovic, N. L. (2002). Innate Direct Anticancer Effector Function of Human Immature Dendritic Cells. II. Role of TNF, Lymphotoxin-{alpha}1{beta}2, Fas Ligand, and TNF-Related Apoptosis-Inducing Ligand. J. Immunol. 168: 1831-1839 [Abstract] [Full Text]  
• Loza, M. J., Zamai, L., Azzoni, L., Rosati, E., Perussia, B. (2002). Expression of type 1 (interferon gamma) and type 2 (interleukin-13, interleukin-5) cytokines at distinct stages of natural killer cell differentiation from progenitor cells. Blood 99: 1273-1281 [Abstract] [Full Text]  
• Choi, C., Kutsch, O., Park, J., Zhou, T., Seol, D.-W., Benveniste, E. N. (2002). Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Induces Caspase-Dependent Interleukin-8 Expression and Apoptosis in Human Astroglioma Cells. Mol. Cell. Biol. 22: 724-736 [Abstract] [Full Text]  
• Meng, X. W., Heldebrant, M. P., Kaufmann, S. H. (2002). Phorbol 12-myristate 13-Acetate Inhibits Death Receptor-mediated Apoptosis in Jurkat Cells by Disrupting Recruitment of Fas-associated Polypeptide with Death Domain. J. Biol. Chem. 277: 3776-3783 [Abstract] [Full Text]  
• Siegmund, D., Hausser, A., Peters, N., Scheurich, P., Wajant, H. (2001). Tumor Necrosis Factor (TNF) and Phorbol Ester Induce TNF-related Apoptosis-inducing Ligand (TRAIL) under Critical Involvement of NF-kappa B Essential Modulator (NEMO)/IKKgamma. J. Biol. Chem. 276: 43708-43712 [Abstract] [Full Text]  
• Taylor, M. A., Chaudhary, P. M., Klem, J., Kumar, V., Schatzle, J. D., Bennett, M. (2001). Inhibition of the Death Receptor Pathway by cFLIP Confers Partial Engraftment of MHC Class I-Deficient Stem Cells and Reduces Tumor Clearance in Perforin-Deficient Mice. J. Immunol. 167: 4230-4237 [Abstract] [Full Text]  
• Secchiero, P., Gonelli, A., Celeghini, C., Mirandola, P., Guidotti, L., Visani, G., Capitani, S., Zauli, G. (2001). Activation of the nitric oxide synthase pathway represents a key component of tumor necrosis factor-related apoptosis-inducing ligand-mediated cytotoxicity on hematologic malignancies. Blood 98: 2220-2228 [Abstract] [Full Text]  
• Powzaniuk, M. A., Trotta, R., Loza, M. J., Harth, A., Iozzo, R. V., Eisenlohr, L. C., Perussia, B., Calabretta, B. (2001). B-Myb Overexpression Results in Activation and Increased Fas/Fas Ligand-Mediated Cytotoxicity of T and NK Cells. J. Immunol. 167: 242-249 [Abstract] [Full Text]  
• Ogawa, K., Tanaka, K., Ishii, A., Nakamura, Y., Kondo, S., Sugamura, K., Takano, S., Nakamura, M., Nagata, K. (2001). A Novel Serum Protein That Is Selectively Produced by Cytotoxic Lymphocytes. J. Immunol. 166: 6404-6412 [Abstract] [Full Text]  
• Moreau, G., Leite-de-Moraes, M., Ezine, S., Di Santo, J. P., Dy, M., Schneider, E. (2001). Natural killer cell-dependent apoptosis of peripheral murine hematopoietic progenitor cells in response to Fas cross-linking: involvement of tumor necrosis factor-{alpha}. Blood 97: 3069-3074 [Abstract] [Full Text]  
• Di Pietro, R., Secchiero, P., Rana, R., Gibellini, D., Visani, G., Bemis, K., Zamai, L., Miscia, S., Zauli, G. (2001). Ionizing radiation sensitizes erythroleukemic cells but not normal erythroblasts to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated cytotoxicity by selective up-regulation of TRAIL-R1. Blood 97: 2596-2603 [Abstract] [Full Text]  
• Smyth, M. J., Cretney, E., Takeda, K., Wiltrout, R. H., Sedger, L. M., Kayagaki, N., Yagita, H., Okumura, K. (2001). Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) Contributes to Interferon {{gamma}}-dependent Natural Killer Cell Protection from Tumor Metastasis. JEM 193: 661-670 [Abstract] [Full Text]  
• Brill, K. J., Li, Q., Larkin, R., Canaday, D. H., Kaplan, D. R., Boom, W. H., Silver, R. F. (2001). Human Natural Killer Cells Mediate Killing of Intracellular Mycobacterium tuberculosis H37Rv via Granule-Independent Mechanisms. Infect. Immun. 69: 1755-1765 [Abstract] [Full Text]  
• Yu, Y., Hagihara, M., Ando, K., Gansuvd, B., Matsuzawa, H., Tsuchiya, T., Ueda, Y., Inoue, H., Hotta, T., Kato, S. (2001). Enhancement of Human Cord Blood CD34+ Cell-Derived NK Cell Cytotoxicity by Dendritic Cells. J. Immunol. 166: 1590-1600 [Abstract] [Full Text]  
• Wang, R., Zhang, L., Zhang, X., Moreno, J., Luo, X., Tondravi, M., Shi, Y. (2001). Differential Regulation of the Expression of CD95 Ligand, Receptor Activator of Nuclear Factor-{{kappa}}B Ligand (RANKL), TNF-Related Apoptosis-Inducing Ligand (TRAIL), and TNF-{{alpha}} During T Cell Activation. J. Immunol. 166: 1983-1990 [Abstract] [Full Text]  
• Austin Taylor, M., Bennett, M., Kumar, V., Schatzle, J. D. (2000). Functional Defects of NK Cells Treated with Chloroquine Mimic the Lytic Defects Observed in Perforin-Deficient Mice. J. Immunol. 165: 5048-5053 [Abstract] [Full Text]  
• Trinite, B., Voisine, C., Yagita, H., Josien, R. (2000). A Subset of Cytolytic Dendritic Cells in Rat. J. Immunol. 165: 4202-4208 [Abstract] [Full Text]  
• Brandau, S., Suttmann, H., Riemensberger, J., Seitzer, U., Arnold, J., Durek, C., Jocham, D., Flad, H.-D., Böhle, A. (2000). Perforin-mediated Lysis of Tumor Cells by Mycobacterium Bovis Bacillus Calmette-Guerin-activated Killer Cells. Clin. Cancer Res. 6: 3729-3738 [Abstract] [Full Text]  
• Zamai, L., Secchiero, P., Pierpaoli, S., Bassini, A., Papa, S., Alnemri, E. S., Guidotti, L., Vitale, M., Zauli, G. (2000). TNF-related apoptosis-inducing ligand (TRAIL) as a negative regulator of normal human erythropoiesis. Blood 95: 3716-3724 [Abstract] [Full Text]  
• Raziuddin, A., Bennett, M., Winkler-Pickett, R., Ortaldo, J. R., Longo, D. L., Murphy, W. J. (2000). Synergistic effects of in vivo depletion of Ly-49A and Ly-49G2 natural killer cell subsets in the rejection of H2b bone marrow cell allografts. Blood 95: 3840-3844 [Abstract] [Full Text]  
• Berthou, C., Bourge, J.-F., Zhang, Y., Soulie, A., Geromin, D., Denizot, Y., Sigaux, F., Sasportes, M. (2000). Interferon-gamma -induced membrane PAF-receptor expression confers tumor cell susceptibility to NK perforin-dependent lysis. Blood 95: 2329-2336 [Abstract] [Full Text]  
• Kashii, Y., Giorda, R., Herberman, R. B., Whiteside, T. L., Vujanovic, N. L. (1999). Constitutive Expression and Role of the TNF Family Ligands in Apoptotic Killing of Tumor Cells by Human NK Cells. J. Immunol. 163: 5358-5366 [Abstract] [Full Text]  
• Kayagaki, N., Yamaguchi, N., Nakayama, M., Takeda, K., Akiba, H., Tsutsui, H., Okamura, H., Nakanishi, K., Okumura, K., Yagita, H. (1999). Expression and Function of TNF-Related Apoptosis-Inducing Ligand on Murine Activated NK Cells. J. Immunol. 163: 1906-1913 [Abstract] [Full Text]  
• Sedger, L. M., Shows, D. M., Blanton, R. A., Peschon, J. J., Goodwin, R. G., Cosman, D., Wiley, S. R. (1999). IFN-{gamma} Mediates a Novel Antiviral Activity Through Dynamic Modulation of TRAIL and TRAIL Receptor Expression. J. Immunol. 163: 920-926 [Abstract] [Full Text]  
• Smyth, M. J., Thia, K. Y. T., Cretney, E., Kelly, J. M., Snook, M. B., Forbes, C. A., Scalzo, A. A. (1999). Perforin Is a Major Contributor to NK Cell Control of Tumor Metastasis. J. Immunol. 162: 6658-6662 [Abstract] [Full Text]  
• Muhlenbeck, F., Schneider, P., Bodmer, J.-L., Schwenzer, R., Hauser, A., Schubert, G., Scheurich, P., Moosmayer, D., Tschopp, J., Wajant, H. (2000). The Tumor Necrosis Factor-related Apoptosis-inducing Ligand Receptors TRAIL-R1 and TRAIL-R2 Have Distinct Cross-linking Requirements for Initiation of Apoptosis and Are Non-redundant in JNK Activation. J. Biol. Chem. 275: 32208-32213 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS