Skip to main content

Advertisement

SpringerLink
Log in

Role of TNF superfamily ligands in innate immunity

  • UNIVERSITY OF PITTSBURGH IMMUNOLOGY 2011
  • Published:
Immunologic Research Aims and scope Submit manuscript

Abstract

Natural killer (NK) cells and dendritic cells (DCs) are essential effector cells of the innate immune system that rapidly recognize and eliminate microbial pathogens and abnormal cells, and induce and regulate adaptive immune functions. While NK cells express perforin and granzymes in the lysosomal granules and transmembrane tumor necrosis factor superfamily ligands (tmTNFSFL) on the plasma membrane, DCs express only tmTNFSFL on the plasma membrane. Perforin and granzymes are cytolytic molecules, which NK cells use to mediate a secretory/necrotic killing mechanism against rare leukemia cell targets. TNFSFL are pleiotropic transmembrane molecules, which can mediate a variety of important functions such as apoptosis, development of peripheral lymphoid tissues, inflammation and regulation of immune functions. Using tmTNFSFL, NK cells and DCs mediate a cell contact-dependent non-secretory apoptotic cytotoxic mechanism against virtually all types of cancer cells, and cross talk that leads to polarization and reciprocal stimulation and amplification of Th1 type cytokines secreted by NK cells and DCs. In this paper, we review and discuss the supporting evidence of the non-secretory, tmTNFSFL-mediated innate mechanisms of NK cells and DCs, their roles in anticancer immune defense and potential of their modulation and use in prevention and treatment of cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Arch RH, Gedrich RW, Thompson CB. Tumor necrosis factor receptor-associated factors (TRAFs)—a family of adapter proteins that regulates life and death. Genes Dev. 1998;12:2821–30.

    PubMed  CAS  Google Scholar 

  2. Beutler B, van Huffel C. Unraveling function in the TNF ligand and receptor families. Science. 1994;264:667–8.

    PubMed  CAS  Google Scholar 

  3. Muppidi JR, Tschopp J, Siegel RM. Life and death decisions: secondary complexes and lipid rafts in TNF receptor family signal transduction. Immunity. 2004;21:461–5.

    PubMed  CAS  Google Scholar 

  4. Smith CA, Farrah T, Goodwin RG. The TNF receptor superfamily of cellular and viral proteins: activation, costimulation, and death. Cell. 1994;76:959–69.

    PubMed  CAS  Google Scholar 

  5. Vujanovic NL. Role of TNF family ligands in antitumor activity of natural killer cells. Internat Rev Immunol. 2001;20:415–35.

    CAS  Google Scholar 

  6. Vujanovic NL, Nagashima S, Herberman RB, et al. Cytotoxic mechanisms of natural killer cells. In: Lukic M, Dujic A, Cuperlovic K, editors. Immunoregulation in health and disease-experimental and clinical aspects. New York: Acad Press; 1997. p. 349–67.

    Google Scholar 

  7. Green DR, Droin N, Pinkoski M. Activation induced cell death in T cells. Immunol Rev. 2003;193:70–81.

    PubMed  CAS  Google Scholar 

  8. Demeter J, Ramisch S, et al. Polymorphism of the tumor necrosis factor-alpha and lymphotoxin-alpha genes in chronic lymphocytic leukemia. Brit J Hematol. 1997;97:107–12.

    CAS  Google Scholar 

  9. Drappa J, Vaishnaw AK, Sullivan KE, et al. Fas gene mutations in the Canale-Smith syndrome, an inherited lymphoproliferative disorder associated with autoimmunity. N Engl J Med. 1996;335:1643–9.

    PubMed  CAS  Google Scholar 

  10. Davidson WF, Giese T, Fredrickson TN. Spontaneous development of plasmocytoid tumors in mice with defective Fas-Fas ligand interactions. J Exp Med. 1998;187:1825–38.

    PubMed  CAS  Google Scholar 

  11. Landowski TH, Ou N, Buyksal I, et al. Mutations in the Fas antigen in patients with multiple myeloma. Blood. 1997;90:4266–70.

    PubMed  CAS  Google Scholar 

  12. Smyth MJ, Kelly JM, Baxter AG, et al. An essential role of tumor necrosis factor in natural killer cell-mediated tumor rejection in the peritoneum. J Exp Med. 1998;188:1611–9.

    PubMed  CAS  Google Scholar 

  13. Ito D, Back TC, Shakhov AN, et al. Mice with a targeted mutation in lymphotoxin-α exhibit enhanced tumor growth and metastases: Impaired NK cell development and recruitment. J Immunol. 1999;163:2809–15.

    PubMed  CAS  Google Scholar 

  14. Hayward AR, Levy J, Facchetii F, et al. Cholangiopathy and tumors of the pancreas, liver and biliary tree in boys with X-linked immunodeficiency with hyper-IgM. J Immunol. 1997;158:977–83.

    PubMed  CAS  Google Scholar 

  15. Ostenstand B, Giliani S, Mellbye OJ, et al. A boy with X-linked hyper-IgM syndrome and natural killer cell deficiency. Clin Exp Immunol. 1997;107:230–4.

    Google Scholar 

  16. Djerbi M, Screpanti MV, Catrina AI, et al. The inhibitor of death receptor signaling, FLICE-inhibitory protein defines a new class of tumor progression factors. J Exp Med. 1999;190:1025–31.

    PubMed  CAS  Google Scholar 

  17. French LE, Tshopp J. Inhibition of death receptor signaling by FLICE-inhibitory protein as a mechanism for immune escape of tumors. J Exp Med. 1999;190:891–3.

    PubMed  CAS  Google Scholar 

  18. Medema JP, Jong Jd, Hall Tv, et al. Immune escape of tumors in vivo by expression of cellular FLICE-inhibitory protein. J Exp Med. 1999;190:133–8.

    Google Scholar 

  19. Takeda K, Hayakawa Y, Smyth MJ, et al. Involvement of tumor necrosis factor-related apoptosis-inducing ligand in surveillance of tumor metastasis by liver natural killer cells. Nature Med. 2001;7:94–100.

    PubMed  CAS  Google Scholar 

  20. Qin Z, Blankenstein T. Tumor growth inhibition by lymphotoxin: evidence of B lymphocyte involvement in the antitumor response. Cancer Res. 1995;55:4747–51.

    PubMed  CAS  Google Scholar 

  21. Schrama D, Straten PT, Fischer WH, et al. Targeting of lymphotoxin-α to the tumor elicits an efficient immune response associated with induction of peripheral lymphoid-like tissue. Immunity. 2001;14:111–21.

    PubMed  CAS  Google Scholar 

  22. Latinis KM, Carr LL, Peterson EJ, et al. Regulation of CD95 (Fas) ligand expression by TCR-mediated signaling events. J Immunol. 1997;158:4602–11.

    PubMed  CAS  Google Scholar 

  23. Bossi G, Griffiths GM. Degranulation plays an essential part in regulating cell surface expression of Fas ligand in T cells and natural killer cells. Nature Med. 1999;5:90–6.

    PubMed  CAS  Google Scholar 

  24. Dao T, Ohashi K, Kayano T, et al. Interferon-gamma-inducing factor, a novel cytokine, enhances Fas ligand-mediated cytotoxicity of murine T helper 1 cells. Cell Immunol. 1996;173:230–5.

    PubMed  CAS  Google Scholar 

  25. Fanger NA, Maliszewski CR, Schooley K, et al. Human dendritic cells mediate cellular apoptosis via tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). J Exp Med. 1999;190:1155–64.

    PubMed  CAS  Google Scholar 

  26. Griffith TS, Wiley SR, Kubin MZ. Monocyte-mediated tumoricidal activity via the tumor necrosis factor-related cytokine, TRAIL. J Exp Med. 1999;189:1343–53.

    PubMed  CAS  Google Scholar 

  27. Kayagaki N, Yamaguchi N, Nakayama M, et al. Type I interferons (IFNs) regulate tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) expression on human T cells: A novel mechanism for the antitumor effects of type I IFNs. J Exp Med. 1999;189:1451–560.

    PubMed  CAS  Google Scholar 

  28. Medvedev AE, Johnsen AC, Haux J, et al. Regulation of Fas and Fas-ligand expression in NK cells by cytokines and the involvement of Fas-ligand in NK/LAK cell-mediated cytotoxicity. Cytokine. 1997;9:394–404.

    PubMed  CAS  Google Scholar 

  29. Smyth MJ, Creteney E, Takeda K, et al. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) contributes to interferon γ-dependent natural killer cell protection from tumor metastasis. J Exp Med. 2001;193:661–70.

    PubMed  CAS  Google Scholar 

  30. Fellenberg J, Mau H, Scheuerpflug C, et al. Modulation of resistance to anti-Apo-1-induced apoptosis in osteosarcoma cells by cytokines. Int J Cancer. 1997;72:536–42.

    PubMed  CAS  Google Scholar 

  31. Ossima NK, Cannas A, Powers VC, et al. Interferon-γ modulates a p53-independent apoptotic pathway and apoptosis-related gene expression. J Biol Chem. 1997;272:16351–7.

    Google Scholar 

  32. Lu G, Janjic BM, Janjic J, et al. Innate direct anticancer effector function of human immature dendritic cells. II. Role of TNF, LT-α1β2, FasL and TRAIL. J Immunol. 2002;168:1831–9.

    PubMed  CAS  Google Scholar 

  33. Black RA, Rauch CT, Kozlosky CJ, et al. A metalloproeinase disintegrin that releases tumor-necrosis factor-α from cells. Nature. 1997;385:729–33.

    PubMed  CAS  Google Scholar 

  34. Gearing AJH, Beckett P, Christodoulou M, et al. Processing of tumor necrosis factor-α precursor by metalloproteinases. Nature. 1994;370:555–7.

    PubMed  CAS  Google Scholar 

  35. Kayagaki N, Kawasaki A, Ebata T, et al. Metalloproteinase-mediated release of human Fas ligand. J Exp Med. 1995;182:1777–83.

    PubMed  CAS  Google Scholar 

  36. Reddy P, Slack JL, Davis R, et al. Functional analysis of the domain structure of tumor necrosis factor-α concerting enzyme. J Biol Chem. 2000;275:14608–14.

    PubMed  CAS  Google Scholar 

  37. Suda T, Hashimoto H, Tanaka M, et al. Membrane Fas ligand kills human peripheral blood T lymphocytes, and soluble Fas ligand blocks the killing. J Exp Med. 1997;186:2045–50.

    PubMed  CAS  Google Scholar 

  38. Tanaka M, Itai T, Adachi M, et al. Downregulation of Fas ligand by shedding. Nat Med. 1998;4:31–6.

    PubMed  CAS  Google Scholar 

  39. Kashii Y, Giorda R, Herberman RB, et al. Constitutive expression and role of the TNF family ligands in apoptotic killing by human NK cells. J Immunol. 1999;163:5358–66.

    PubMed  CAS  Google Scholar 

  40. Aderka D, Englemann H, Hornik V, et al. Increased serum levels of soluble receptors for tumor necrosis factor in cancer patients. Cancer Res. 1991;51:5602–7.

    PubMed  CAS  Google Scholar 

  41. Gatanaga T, Hwang CD, Kohr W, et al. Purification and characterization of an inhibitor (soluble tumor necrosis factor receptor) for tumor necrosis factor and lymphotoxin obtained from the serum ultrafiltrates of human cancer patients. Proc Natl Acad Sci USA. 1990;87:8781–4.

    PubMed  CAS  Google Scholar 

  42. Kaminska J, Nowacki MP, Kowalska M, et al. Clinical significance of serum cytokine measurements in untreated colorectal cancer patients: soluble tumor necrosis factor receptor type I—an independent prognostic factor. Tumor Biol. 2005;26:186–94.

    CAS  Google Scholar 

  43. Shibata M, Takekawa M, Amano S. Increased serum concentrations of soluble tumor necrosis factor receptor I in noncachectic and cachectic patients with advanced gastric and colorectal cancer. Surg Today. 1998;28:884–8.

    PubMed  CAS  Google Scholar 

  44. Ge L, Baskic D, Basse P, et al. Sheddase activity of tumor necrosis factor-a converting enzyme is increase and prognostically valuable in head and neck cancer. Cancer Epidemiol Biomarkers Prev. 2009;18:2913–22.

    PubMed  CAS  Google Scholar 

  45. Hohlbaum AM, Moe S, Marshak-Rothstein A. Opposing effects of transmembrane and soluble Fas ligand expression on inflamation and tumor cell survival. J Exp Med. 2000;191:1209–19.

    PubMed  CAS  Google Scholar 

  46. Wallach D, Varfolmeev EE, Malinin NL, et al. Tumor necrosis factor receptor and Fas signaling mechanisms. Annu Rev Immunol. 1999;17:331–67.

    PubMed  CAS  Google Scholar 

  47. Pasparakis M, Alexopoulou L, Episkopou V, et al. Immune and inflammatory responses in TNF alpha-deficient mice: a critical requirement for TNF alpha in the formation of primary B cell follicles, follicular dendritic cell networks and germinal centers, and in the maturation of the humoral immune response. J Exp Med. 1996;184:1397–411.

    PubMed  CAS  Google Scholar 

  48. Mueller C, Corazza N, Trachsel-Loseth S, et al. Noncleavable transmembrane mouse tumor necrosis factor-alpha (TNFalpha) mediates effects distinct from those of wild-type TNFalpha in vitro and in vivo. J Biol Chem. 1999;274:38112–8.

    PubMed  CAS  Google Scholar 

  49. Alexopoulou L, Kranidioti K, Xanthoulea S, et al. Transmembrane TNF protects mutant mice against intracellular bacterial infections, chronic inflammation and autoimmunity. Eur J Immunol. 2006;36:2768–80.

    PubMed  CAS  Google Scholar 

  50. Canault M, Peiretti F, Mueller C, et al. Exclusive expression of transmembrane TNF-alpha in mice reduces the inflammatory response in early lipid lesions of aortic sinus. Atherosclerosis. 2004;172:211–8.

    PubMed  CAS  Google Scholar 

  51. Cauwels A, Molle WV, Janssen B, et al. Protection against TNF-induced lethal shock by soluble guanylate cyclase inhibition requires functional inducible nitric oxide synthase. Immunity. 2000;13:223–31.

    PubMed  CAS  Google Scholar 

  52. Cope AP, Liblau RS, Yang X-D, et al. Chronic tumor necrosis factor alters T cell responses by attenuating T cell receptor signaling. J Exp Med. 1997;185:1573–84.

    PubMed  CAS  Google Scholar 

  53. Isomaki P, Panesar M, Annenkov A, et al. Prolonged exposure of T cells to TNF down-regulates TCRζ and expression of the TCR/CD3 complex at the cell surface. J Immunol. 2001;166:5495–507.

    PubMed  CAS  Google Scholar 

  54. Ruuls SR, Hoek RM, Ngo VN, et al. Membrane-bound TNF supports secondary lymphoid organ structure but is subservient to secreted TNF in driving autoimmune inflammation. Immunity. 2001;15:533–43.

    PubMed  CAS  Google Scholar 

  55. Saunders BM, Tran S, Ruuls S, et al. Transmembrane TNF is sufficient to initiate cell migration and granuloma formation and provide acute, but not long-term, control of Mycobacterium tuberculosis infection. J Immunol. 2005;174:4852–9.

    PubMed  CAS  Google Scholar 

  56. Tanaka M, Suda T, Yatomi T, et al. Lethal effect of recombinant human Fas ligand in mice pretreated with Propionibacterium acnes. J Immunol. 1997;158:2303–9.

    PubMed  CAS  Google Scholar 

  57. Wajant H, Pfitzenmaier K, Scheurich P. Tumor necrosis factor signaling. Cell Death Differ. 2003;10:45–65.

    PubMed  CAS  Google Scholar 

  58. Wong M, Ziring D, Korin Y, et al. TNFalpha blockade in human diseases: mechanisms and future directions. Clin Immunol. 2008;128:121–36.

    Google Scholar 

  59. Trinchieri G. Biology of natural killer cells. Adv Immunol. 1989;47:187–376.

    PubMed  CAS  Google Scholar 

  60. Moretta L, Bottino C, Ferlazzo G. Surface receptors and functional interactions of human natural killer cells: from bench to the clinic. Cell Mol Life Sci. 2003;60:2139–46.

    PubMed  CAS  Google Scholar 

  61. Gorelik E, Herberman RB. Role of natural killer (NK) cells in control of tumor growth and metastatic spread. In: Herberman RB, editor. Cancer immunology: inovative approaches to therapy. Boston: Martinus Nijhoff Publishers; 1986. p. 152–76.

    Google Scholar 

  62. Gorelik E, Rosen D, Copeland D, et al. Evaluation of the role of natural killer cells in radiation-induced leukemogenesis in mice. J Natl Cancer Inst. 1984;72:1397–403.

    PubMed  CAS  Google Scholar 

  63. Ricardi C, Barlozzari T, Santoni A, et al. Transfer of cyclophosphamide-treated mice natural killer (NK) cells and in vivo natural reactivity against tumors. J Immunol. 1981;126:1284–9.

    Google Scholar 

  64. Wiltrout RH, Herberman RB, Zhang S-R, et al. Role of organ-associated NK cells in decreased formation of experimental metastases in lung and liver. J Immunol. 1985;134:4267–75.

    PubMed  CAS  Google Scholar 

  65. Vujanovic NL, Nagashima S, Herberman RB, et al. Non-secretory apoptotic killing by human natural killer cells. J Immunol. 1996;157:1117–26.

    PubMed  CAS  Google Scholar 

  66. Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature. 1998;392:245–52.

    PubMed  CAS  Google Scholar 

  67. King PD, Katz DR. Mechanisms of dendritic cell function. Immunol Today. 1990;11:206–11.

    PubMed  CAS  Google Scholar 

  68. Steinman RM. The dendritic cell system and its role in immunogenicity. Annu Rev Immunol. 1991;9:271–96.

    PubMed  CAS  Google Scholar 

  69. Albert ML, Pierce SFA, Francisco LM, et al. Immature dendritic cells phagocytose apoptotic cells via αvβ5 and CD36, and cross-present antigens to cytotoxic T lymphocytes. J Exp Med. 1998;188:1359–68.

    PubMed  CAS  Google Scholar 

  70. Albert ML, Sauter B, Bhardwaj N. Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs. Nature. 1998;392:86–9.

    PubMed  CAS  Google Scholar 

  71. Hoffman TK, Meidenbauer N, Dworacki G, et al. Generation of tumor-specific T lymphocytes by cross-priming with human dendritic cells ingesting apoptotic tumor cells. Cancer Res. 2000;60:3542–9.

    Google Scholar 

  72. Inaba K, Turley S, Yamaide F, et al. Efficient presentation of phagocytosed cellular fragments on the major histocompatibility complex class II products of dendritic cells. J Exp Med. 1998;188:2163–73.

    PubMed  CAS  Google Scholar 

  73. Ronchetti A, Rovere P, Iezzi G, et al. Immunogenicity of apoptotic cells in vivo: Role of antigen load, antigen-presenting cells, and cytokines. J Immunol. 1999;163:130–6.

    PubMed  CAS  Google Scholar 

  74. Sauter B, Albert ML, Francisco L, et al. Consequences of cell death: exposure to necrotic tumor cells, but not primary tissue cells or apoptotic cells, induces the maturation of immunostimulatory dendritic cells. J Exp Med. 2000;191:423–34.

    PubMed  CAS  Google Scholar 

  75. Zitvogel L, Mayordomo JL, Tjandrawan T, et al. Therapy of murine tumors with tumor peptide-pulsed dendritic cells: dependence on T cells, B7 costimulation, and Th1-associated cytokines. J Exp Med. 1996;183:87–97.

    PubMed  CAS  Google Scholar 

  76. Liu S, Yu Y, Zhang M, et al. The involvement of TNF-α-related apoptosis-inducing ligand in the enhanced cytotoxicity of IFN-β-stimulated human dendritic cells to tumor cells. J Immunol. 2001;166:5407–15.

    PubMed  CAS  Google Scholar 

  77. Becker Y. Dendritic cell activity against primary tumors: an overview. In Vivo. 1993;7:187–91.

    PubMed  CAS  Google Scholar 

  78. Janjic BM, Lu G, Pimenov A, et al. Innate direct anticancer effector function of human immature dendritic cells. I. Involvement of a potent apoptosis-inducing pathway. J Immunol. 2002;168:1823–30.

    PubMed  CAS  Google Scholar 

  79. Andrews DM, Scalzo AA, Yokoyama WM, et al. Functional interactions between dendritic cells and NK cells during viral infection. Nat Immunol. 2003;4:175–81.

    PubMed  CAS  Google Scholar 

  80. Ferlazzo G, Munz C. NK cell compartments and their activation by dendritic cells. J Immunol. 2004;172:1333–9.

    PubMed  CAS  Google Scholar 

  81. Ferlazzo G, Tsang ML, Morretta L, et al. Human dendritic cells activate resting natural killer (NK) cells and are recognized via NKp30 receptor by activated NK cells. J Exp Med. 2002;195:343–51.

    PubMed  CAS  Google Scholar 

  82. Fernandez NC, Lozier A, Flament C, et al. Dendritic cells directly trigger NK cell functions: Cross-talk relevant in innate anti-tumor immune responses in vivo. Nat Med. 1999;5:405–11.

    PubMed  CAS  Google Scholar 

  83. Gerosa F, Baldani-Guerra B, Nisii C, et al. Reciprocal activating interaction between natural killer cells and dendritic cells. J Exp Med. 2002;195:327–33.

    PubMed  CAS  Google Scholar 

  84. Goodier M, Londei M. Lipopolysaccharide stimulates the proliferation of human CD56+CD3− NK cells: A regulatory role of monocytes and IL-10. J Immunol. 2000;165:139–47.

    PubMed  CAS  Google Scholar 

  85. Jinushi M, Takehara T, Kanto T. Critical role of MHC class I-related chain A and B expression on IFN-alpha stimulated dendritic cells in NK cell activation: Impairment in chronic hepatitis C virus infection. J Immunol. 2003;170:1249–56.

    PubMed  CAS  Google Scholar 

  86. Kalinski P, Maillard RB, Giermasz A. Natural killer-dendritic cell cross-talk in cancer immunotherapy. Expert Opin Biol Ther. 2005;5:1303–15.

    PubMed  CAS  Google Scholar 

  87. Mailliard RB, Son Y-I, Redlinger R, et al. Dendritic cells mediate NK cell help for Th1 and CTL responses: Two-signal requirement for the induction of NK cell helper function. J Immunol. 2003;171:2366–73.

    PubMed  CAS  Google Scholar 

  88. Moretta A. Natural killer cells and dendritic cells:randezvous in abused tissues. Nat Rev Immunol. 2002;2:957–64.

    PubMed  CAS  Google Scholar 

  89. Moretta A, Marcenaro E, Sivori S, et al. Early liaisons between cells of the innate immune system in inflamed peripheral tissues. TRENDS Immunol. 2005;26:668–75.

    PubMed  CAS  Google Scholar 

  90. Osada T, Nagawa H, Kitayama J, et al. Peripheral blood dendritic cells, but not monocyte-derived dendritic cells, can augment human NK cell function. Cell Immunol. 2001;213:14–23.

    PubMed  CAS  Google Scholar 

  91. Piccioli D, Sbrana S, Melandri E, et al. Contact-dependent stimulation and inhibition of dendritic cells by natural killer cells. J Exp Med. 2002;195:335–41.

    PubMed  CAS  Google Scholar 

  92. Poggi A, Carosio R, Spaggiari GM, et al. NK cell activation of dendritic cells is dependent on LFA-1-mediated induction of calcium-calmodulin kinase II: inhibition by HIV-1 Tar C-terminal domain. J Immunol. 2002;168:95–101.

    PubMed  CAS  Google Scholar 

  93. Yu Y, Hagihara M, Ando K, et al. Enhancment of human cord blood CD34+ cell-derived NK cell cytotoxicity by dendritic cells. J Immunol. 2001;166:1590–600.

    PubMed  CAS  Google Scholar 

  94. Carbone E, Terrazzano G, Ruggiero G, et al. Recognition of autologous dendritic cells by human NK cells. Eur J Immunol. 1999;29:4022–9.

    PubMed  CAS  Google Scholar 

  95. Chiesa MD, Vitale M, Carlomagno S, et al. The natural killer cell-mediated killing of autologous dendritic cells is confined to a cell subset expressin CD94/NKG2A, but lacking inhibitory killer Ig-like receptors. Eur J Immunol. 2003;33:1654–66.

    Google Scholar 

  96. Ferlazzo G, Morandi B, D’Agostino A, et al. The interaction between NK cells and dendritic cells in bacterial infections results in rapid induction of NK cell activation and in the lysis of uninfected dendritic cells. Eur J Immunol. 2003;33:306–13.

    PubMed  CAS  Google Scholar 

  97. Ferlazzo G, Semino C, Melioli G, et al. HLA class I molecule expression is up-regulated during maturation of dendritic cells, protecting them from natural killer cell-mediated lysis. Immunol Lett. 2001;76:34–41.

    Google Scholar 

  98. Geldhof AB, Moser M, Lespagnard L, et al. Interleukin-12-activated natural killer cells recognize B7 costimulatory molecules on tumor cells and autologous dendritic cells. Blood. 1998;91:196–206.

    PubMed  CAS  Google Scholar 

  99. Hayakawa Y, Screpanti V, Yagita H, et al. NK cell TRAIL eliminates immature dendritic cells in vivo and limits dendritic cell vaccination efficacy. J Immunol. 2004;172:123–9.

    PubMed  CAS  Google Scholar 

  100. Spaggiari GM, Carosio R, Pende D, et al. NK cell mediated lysis of autologous antigen presenting cells is triggered by the engagement of the phosphatidylinositol 3-kinase upon ligation of the natural cytotoxicity receptors NKp30a nad NKp46. Eur J Immunol. 2001;3:1656–65.

    Google Scholar 

  101. Cooper MA, Fehniger TA, Caligiuri MA. The biology of human natural killer-cell subsets. TRENDS Immunol. 2001;22:633–40.

    PubMed  CAS  Google Scholar 

  102. Cooper MA, Fehniger TA, Fuchs A. NK cell and DC interactions. TRENDS Immunol. 2004;25:47–52.

    PubMed  CAS  Google Scholar 

  103. Vujanovic NL. Testing natural killer cells. In: Lotze MT, Thomson AW, editors. Measuring immunity. New York: Academic Press, Elsevier Science; 2004. p. 396–403.

    Google Scholar 

  104. Li S, Xu J, Makarenkova VP, et al. A novel epitope of N-CAM defines precursors of human adherent NK cells. J Leuk Biol. 2004;76:1187–99.

    CAS  Google Scholar 

  105. Lanier LL, Phillips JH. Natural killer cells. Curr Opin Immunol. 1992;4:38–42.

    PubMed  CAS  Google Scholar 

  106. Robertson MJ, Ritz J. Biology and clinical relevance of human NK cells. Blood. 1990;76:2421–38.

    PubMed  CAS  Google Scholar 

  107. Ruggeri L, Capanni M, Urbani E, et al. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopietic transplants. Science. 2002;295:2097–100.

    PubMed  CAS  Google Scholar 

  108. Yokoyama WM, Plougastel BFM. Immune function encoded by the natural killer gene complex. Nature Rev Immunol. 2003;3:304–16.

    CAS  Google Scholar 

  109. Bramson WY. Role of dendritic cell-derived cytokines in immune regulation. Current Pharm Des. 2001;7:977–92.

    Google Scholar 

  110. Stager S, Kaye PM. CD8+ T-cell priming regulated by cytokines of the innate immune system. Trends Mol Med. 2004;10:366–71.

    PubMed  Google Scholar 

  111. Trinchieri G, Pflanz S, Kastelein RA. The IL-12 family of heterodimeric cytokines: New players in the regulation of T cell responses. Immunity. 2003;19:641–4.

    PubMed  CAS  Google Scholar 

  112. Borg C, Jalil A, Laderach D, et al. NK cell activation by dendritic cells (DCs) requires the formation of a synapse leading to IL-12 polarization in DCs. Blood. 2004;104:3267–75.

    PubMed  CAS  Google Scholar 

  113. Granucci F, Zanoni I, Pavelka N, et al. A contribution of mouse dendritic cell-derived IL-2 for NK cell activation. J Exp Med. 2004;200:287–95.

    PubMed  CAS  Google Scholar 

  114. Rodriguez-Calvillo M, Duarte M, Tirapu I, et al. Upregulation of natural killer cells functions underlies the efficacy of intratumorally injected dendritic cells engineered to produce interleukin-12. Exp Hematol. 2002;30:195–204.

    PubMed  CAS  Google Scholar 

  115. van den Broeke LT, Daschbach E, Thomas EK, et al. Dendritic cell-induced activation of adaptive and innate immunity. J Immunol. 2003;171:5842–52.

    PubMed  Google Scholar 

  116. Vujanovic L, Szymkowski DE, Vujanovic NL, et al. Virally-infected and cytokine-matured human dendritic cells activate natural killer cells via cooperative activity of plasma membrane-bound TNF and IL-15. Blood. 2010;116:575–83.

    PubMed  CAS  Google Scholar 

  117. Makarenkova V, Chakrabarti AK, Liberatore JA, et al. Dendritic cells and natural killer cells interact via multiple TNF family molecules. J Leuk Biol. 2005;77:408–13.

    CAS  Google Scholar 

  118. Xu J, Chakrabarti AK, Tan JA, et al. Essential role of the TNF-TNFR2 cognate interaction in mouse dendritic cell-natural killer cell cross-talk. Blood. 2007;109:3333–41.

    PubMed  CAS  Google Scholar 

  119. Brou C, Logeat F, Gupta N, et al. A novel proteolytic cleavadge involved in notch signaling: the role of the disintegrin-metalloprotease TACE. Mol Cell. 2000;5:207–16.

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

I am grateful to the following previous and current members of my laboratory for their contributions in the presented studies: Bratislav Janjic, Ganwei Lu, Jelena Janjic, Alexei Pimenov and Dejan Baskic (studies of NK cell and DC apoptotic tumoricidal activity); Jun Xu, Valeria Makarenkova, Petar Popovic, Jennifer Liberatore-Tan, Lisheng Ge, Ayan Chakrabarti, Michael Magee, Andrea Sobo-Vujanovic, Toshie Yoneyama and Sebnem Unlu (studies of NK cell/DC cross talk). I am also indebted to the following collaborators: Lazar Vujanovic, Lisa Butterfield, Sigeki Nagashima, Roberto Giorda, Theresa Whiteside, Ronald Herberman, Simon Watkins, Nebojsa Arsenijevic, Per Basse, Eugene Myers, Susan Gollin, Jennifer Hunt and Walter Storkus. In addition, I am obliged to David Szymkowski (XENCOR, Monrovia, CA) who has generously provided us with dominant negative TNF (DN-TNF, XPro1595 and XENP550) reagents. This study was supported by research funding from the National Institute of Health grants I-PO DE13059, RO1 DE14775, RO1 DE17150 and the University of Pittsburgh Cancer Institute and the Henry L. Hillman Foundation to N.L.V.

Author information

Authors and Affiliations

  1. Departments of Pathology and Immunology, University of Pittsburgh, Pittsburgh, PA, USA

    Nikola L. Vujanovic

  2. Hillman Cancer Center, University of Pittsburgh, G.17d, 5117 Centre Avenue, Pittsburgh, PA, 15213-1863, USA

    Nikola L. Vujanovic

Authors
  1. Nikola L. Vujanovic
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nikola L. Vujanovic.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vujanovic, N.L. Role of TNF superfamily ligands in innate immunity. Immunol Res 50, 159–174 (2011). https://doi.org/10.1007/s12026-011-8228-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12026-011-8228-8

Keywords

Search

Navigation