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Cytokine Knockouts pp 439–460Cite as

Physiologic Roles of Members of the TNF and TNF Receptor Families as Revealed by Knockout Models

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Part of the book series: Contemporary Immunology ((CONTIM))

Summary

Members of the tumor necrosis factor (TNF) and TNF receptor (TNFR) families mediate many important functions in the mammalian organism. Ligand-receptor interactions result in signals promoting cell activation, proliferation, inhibition or death. Advances in gene targeting technology continue to uncover biological functions of these molecules in vivo. The review discusses the current state of the field with specific emphasis on the role of TNF and TNFR family members in host defense and their contrasting roles in cancer development and progression. Other features, such as defects in lymphopoiesis, lymphoid organogenesis, and epidermal development are also briefly reviewed.

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References

  1. Carswell, E. A., Old, L. J., Kassel, R. L., Green, S., Fiore, N., and Williamson, B. (1975) An endotoxin-induced serum factor that causes necrosis of tumors. Proc. Natl. Acad. Sci. USA 72, 3666–3670.

    Article  PubMed  CAS  Google Scholar 

  2. Lejeune, F. J., Ruegg, C., and Lienard, D. (1998) Clinical applications of TNF-alpha in cancer. Curr. Opin. Immunol. 10, 573–580.

    Article  PubMed  CAS  Google Scholar 

  3. Gray, P. W., Aggarwal, B. B., Benton, C. V., et al. (1984) Cloning and expression of cDNA for human lymphotoxin, a lymphokine with tumour necrosis activity. Nature 312, 721–724.

    Article  PubMed  CAS  Google Scholar 

  4. Granger, G. A. and Kolb, W. P. (1968) Lymphocyte in vitro cytotoxicity: mechanisms of immune and non-immune small lymphocyte mediated target L cell destruction. J. Immunol. 101, 111–120.

    PubMed  CAS  Google Scholar 

  5. Ruddle, N. H. and Waksman, B. H. (1968) Cytotoxicity mediated by soluble antigen and lymphocytes in delayed hypersensitivity. I. Characterization of the phenomenon. J. Exp. Med. 128, 1237–1254.

    Article  PubMed  CAS  Google Scholar 

  6. Fu, Y. X. and Chaplin, D. D. (1999) Development and maturation of secondary lymphoid tissues. Annu. Rev. Immunol. 17, 399–433.

    Article  PubMed  CAS  Google Scholar 

  7. Locksley, R. M., Killeen, N., and Lenardo, M. J. (2001) The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell 104, 487–501.

    Article  PubMed  CAS  Google Scholar 

  8. Pfeffer, K., Matsuyama, T., Kundig, T. M., et al. (1993) Mice deficient for the 55 kd tumor necrosis factor receptor are resistant to endotoxic shock, yet succumb to L. monocytogenes infection. Cell 73, 457–467.

    Article  PubMed  CAS  Google Scholar 

  9. Rothe, J., Lesslauer, W., Lotscher, H., et al. (1993) Mice lacking the tumour necrosis factor receptor 1 are resistant to TNF-mediated toxicity but highly susceptible to infection by Listeria monocytogenes. Nature 364, 798–802.

    Article  CAS  Google Scholar 

  10. De Togni, P., Goellner, J., Ruddle, N. H., et al. (1994) Abnormal development of peripheral lymphoid organs in mice deficient in lymphotoxin. Science 264, 703–707.

    Article  PubMed  Google Scholar 

  11. Banks, T. A., Rouse, B. T., Kerley, M. K., et al. (1995) Lymphotoxin-alpha-deficient mice. Effects on secondary lymphoid organ development and humoral immune responsiveness. J. Immunol. 155, 1685–1693.

    PubMed  CAS  Google Scholar 

  12. Pasparakis, M., Alexopoulou, L., Episkopou, V., and Kollias, G. (1996) 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. 184, 1397–1411.

    Article  PubMed  CAS  Google Scholar 

  13. Marino, M. W., Dunn, A., Grail, D., et al. (1997) Characterization of tumor necrosis factor-deficient mice. Proc. Natl. Acad. Sci. USA 94, 8093–8098.

    Article  PubMed  CAS  Google Scholar 

  14. Korner, H., Cook, M., Riminton, D. S., et al. (1997) Distinct roles for lymphotoxin-alpha and tumor necrosis factor in organogenesis and spatial organization of lymphoid tissue. Eur. J. Immunol. 27, 2600–2609.

    Article  PubMed  CAS  Google Scholar 

  15. Chen, G. and Goeddel, D. V. (2002) TNF-Rl signaling: a beautiful pathway. Science 296, 1634 1635.

    Google Scholar 

  16. Wajant, H. (2002) The Fas signaling pathway: more than a paradigm. Science 296, 1635–1636.

    Article  PubMed  CAS  Google Scholar 

  17. Roschke, V., Sosnovtseva, S., Ward, C. D., et al. (2002) BLyS and APRIL form biologically active heterotrimers that are expressed in patients with systemic immune-based rheumatic diseases. J. Immunol. 169, 4314–4321.

    PubMed  CAS  Google Scholar 

  18. Yin, L., Wu, L., Wesche, H., et al. (2001) Defective lymphotoxin-beta receptor-induced NF-kappaB transcriptional activity in NIK-deficient mice. Science 291, 2162–2165.

    Article  PubMed  CAS  Google Scholar 

  19. Shinkura, R., Kitada, K., Matsuda, F., et al. (1999) Alymphoplasia is caused by a point mutation in the mouse gene encoding NF-kappa B-inducing kinase. Nat. Genet. 22, 74–77.

    Article  PubMed  CAS  Google Scholar 

  20. Karin, M. and Lin, A. (2002) NF-kappaB at the crossroads of life and death. Nat. Immunol. 3, 221–227.

    Article  PubMed  CAS  Google Scholar 

  21. Senftleben, U., Cao, Y., Xiao, G., et al. (2001) Activation by IKKalpha of a second, evolutionary conserved, NF-kappa B signaling pathway. Science 293, 1495–1499.

    Article  PubMed  CAS  Google Scholar 

  22. Dejardin, E., Droin, N. M., Delhase, M., et al. (2002) The Lymphotoxin-beta receptor induces different patterns of gene expression via two NF-kappaB pathways. Immunity 17, 525–535.

    Article  PubMed  CAS  Google Scholar 

  23. Coope, H. J., Atkinson, P. G., Huhse, B., et al. (2002) CD40 regulates the processing of NF-kappaB2 p100 to p52. EMBO J. 21, 5375–5385.

    Article  PubMed  CAS  Google Scholar 

  24. Kayagaki, N., Yan, M., Seshasayee, D., et al. (2002) BAFF/BLyS Receptor 3 binds the B cell survival factor BAFF ligand through a discrete surface loop and promotes processing of NF-kappaB2. Immunity 17, 515–524.

    Article  PubMed  CAS  Google Scholar 

  25. Janeway, C. A. Jr. and Medzhitov, R. (2002) Innate immune recognition. Annu. Rev. Immunol. 20, 197–216.

    Article  PubMed  CAS  Google Scholar 

  26. Moreno, E., Yan, M., and Basler, K. (2002) Evolution of TNF signaling mechanisms. JNK-dependent apoptosis triggered by Eiger, the Drosophila homolog of the TNF superfamily. Curr. Biol. 12, 1263–1268.

    Article  PubMed  CAS  Google Scholar 

  27. Koni, P. A. and Flavell, R. A. (1998) A role for tumor necrosis factor receptor type 1 in gut-associated lymphoid tissue development: genetic evidence of synergism with lymphotoxin beta. J. Exp. Med. 187, 1977–1983.

    Article  PubMed  CAS  Google Scholar 

  28. Kuprash, D. V., Alimzhanov, M. B., Tumanov, A., Anderson, A. O., Pfeffer, K., and Nedospasov, S. A. (1999) TNF and lymphotoxin beta cooperate in the maintenance of secondary lymphoid tissue microarchitecture but not in the development of lymph nodes. J. Immunol. 163, 6575–6580.

    PubMed  CAS  Google Scholar 

  29. Scheu, S., Alferink, J., Potzel, T., Barchet, W., Kalinke, U., and Pfeffer, K. (2002) Targeted disruption of LIGHT causes defects in costimulatory T cell activation and reveals cooperation with lymphotoxin beta in mesenteric lymph node genesis. J. Exp. Med. 195, 1613–1624.

    Article  PubMed  CAS  Google Scholar 

  30. Kuprash, D. V., Alimzhanov, M. B., Tumanov, A. V., et al. (2002) Redundancy in TNF and LT signaling in vivo: mice with inactivation of the entire TNF/LT locus versus single knockout mice. Mol. Cell. Biol. 22, 8626–8634.

    Article  PubMed  CAS  Google Scholar 

  31. Korner, H., Cretney, E., Wilhelm, P., et al. (2000) Tumor necrosis factor sustains the generalized lymphoproliferative disorder (gld) phenotype. J. Exp. Med. 191, 89–96.

    Article  PubMed  CAS  Google Scholar 

  32. Yan, M., Wang, L. C., Hymowitz, S. G., et al. (2000) Two-amino acid molecular switch in an epithelial morphogen that regulates binding to two distinct receptors. Science 290, 523–527.

    Article  PubMed  CAS  Google Scholar 

  33. Sean Riminton, D., Korner, H., Strickland, D. H., Lemckert, F. A., Pollard, J. D., and Sedgwick, J. D. (1998) Challenging cytokine redundancy: inflammatory cell movement and clinical course of experimental autoimmune encephalomyelitis are normal in lymphotoxin-deficient, but not tumor necrosis factor-deficient, mice. J. Exp. Med. 187, 1517–1528.

    Article  PubMed  CAS  Google Scholar 

  34. Neumann, B., Luz, A., Pfeffer, K., and Holzmann, B. (1996) Defective Peyer’s patch organogenesis in mice lacking the 55-kD receptor for tumor necrosis factor. J. Exp. Med. 184, 259–264.

    Article  PubMed  CAS  Google Scholar 

  35. Le Hir, M., Bluethmann, H., Kosco-Vilbois, M. H., et al. (1996) Differentiation of follicular dendritic cells and full antibody responses require tumor necrosis factor receptor-1 signaling. J. Exp. Med. 183, 2367–2372.

    Article  PubMed  Google Scholar 

  36. Kontoyiannis, D., Pasparakis, M., Pizarro, T. T., Cominelli, F., and Kollias, G. (1999) Impaired on/off regulation of TNF biosynthesis in mice lacking TNF AU- rich elements: implications for joint and gut-associated immunopathologies. Immunity 10, 387–398.

    Article  PubMed  CAS  Google Scholar 

  37. Moore, R. J., Owens, D. M., Stamp, G., et al. (1999) Mice deficient in tumor necrosis factor-alpha are resistant to skin carcinogenesis. Nat. Med. 5, 828–831.

    Article  PubMed  CAS  Google Scholar 

  38. Suganuma, M., Okabe, S., Marino, M. W., Sakai, A., Sueoka, E., and Fujiki, H. (1999) Essential role of tumor necrosis factor alpha (TNF-alpha) in tumor promotion as revealed by TNF-alphadeficient mice. Cancer Res. 59, 4516–4518.

    PubMed  CAS  Google Scholar 

  39. Erickson, S. L., de Sauvage, F. J., Kikly, K., et al. (1994) Decreased sensitivity to tumour-necrosis factor but normal T- cell development in TNF receptor-2-deficient mice. Nature 372, 560–563.

    Article  PubMed  CAS  Google Scholar 

  40. Wang, B., Fujisawa, H., Zhuang, L., et al. (1997) Depressed Langerhans cell migration and reduced contact hypersensitivity response in mice lacking TNF receptor p75. J. Immunol. 159, 6148–6155.

    PubMed  CAS  Google Scholar 

  41. Lucas, R., Juillard, P., Decoster, E., et al. (1997) Crucial role of tumor necrosis factor (TNF) receptor 2 and membrane-bound TNF in experimental cerebral malaria. Eur. J. Immunol. 27, 17191725.

    Google Scholar 

  42. Sam, H., Su, Z., and Stevenson, M. M. (1999) Deficiency in tumor necrosis factor alpha activity does not impair early protective Thl responses against blood-stage malaria. Infect. Immun. 67, 2660–2664.

    PubMed  CAS  Google Scholar 

  43. Ruuls, S. R., Hoek, R. M., Ngo, V. N., et al. (2001) Membrane-bound TNF supports secondary lymphoid organ structure but is subservient to secreted TNF in driving autoimmune inflammation. Immunity 15, 533–543.

    Article  PubMed  CAS  Google Scholar 

  44. Koni, P. A., Sacca, R., Lawton, P., Browning, J. L., Ruddle, N. H., and Flavell, R. A. (1997) Distinct roles in lymphoid organogenesis for lymphotoxins alpha and beta revealed in lymphotoxin beta-deficient mice. Immunity 6, 491–500.

    Article  PubMed  CAS  Google Scholar 

  45. Alimzhanov, M. B., Kuprash, D. V., Kosco-Vilbois, M. H., et al. (1997) Abnormal development of secondary lymphoid tissues in lymphotoxin beta-deficient mice. Proc. Natl. Acad. Sci. USA 94, 9302–9307.

    Article  PubMed  CAS  Google Scholar 

  46. Futterer, A., Mink, K., Luz, A., Kosco-Vilbois, M. H., and Pfeffer, K. (1998) The lymphotoxin beta receptor controls organogenesis and affinity maturation in peripheral lymphoid tissues. Immunity 9, 59–70.

    Article  PubMed  CAS  Google Scholar 

  47. Tumanov, A. V., Kuprash, D. V., Lagarkova, M. A., et al. (2002) Distinct role of surface lymphotoxin expressed by B cells in the organization of secondary lymphoid tissues. Immunity 17, 239–250.

    Article  PubMed  CAS  Google Scholar 

  48. Wu, Q., Wang, Y., Wang, J., Hedgeman, E. O., Browning, J. L., and Fu, Y. X. (1999) The requirement of membrane lymphotoxin for the presence of dendritic cells in lymphoid tissues. J. Exp. Med. 190, 629–638.

    Article  PubMed  CAS  Google Scholar 

  49. Kawabe, T., Naka, T., Yoshida, K., et al. (1994) The immune responses in CD40-deficient mice: impaired immunoglobulin class switching and germinal center formation. Immunity 1, 167–178.

    Article  PubMed  CAS  Google Scholar 

  50. Xu, J., Foy, T. M., Laman, J. D., et al. (1994) Mice deficient for the CD40 ligand. Immunity 1, 423–431.

    Article  PubMed  CAS  Google Scholar 

  51. Renshaw, B. R., Fanslow, W. C. 3rd., Armitage, R. J., et al. (1994) Humoral immune responses in CD40 ligand-deficient mice. J. Exp. Med. 180, 1889–1900.

    Article  PubMed  CAS  Google Scholar 

  52. Grewal, I. S. and Flavell, R. A. (1998) CD40 and CD154 in cell-mediated immunity. Annu. Rev. Immunol. 16, 111–135.

    Article  PubMed  CAS  Google Scholar 

  53. Watanabe-Fukunaga, R., Brannan, C. I., Copeland, N. G., Jenkins, N. A., and Nagata, S. (1992) Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature 356, 314–317.

    Article  PubMed  CAS  Google Scholar 

  54. Takahashi, T., Tanaka, M., Brannan, C. I., et al. (1994) Generalized lymphoproliferative disease in mice, caused by a point mutation in the Fas ligand. Cell 76, 969–976.

    Article  PubMed  CAS  Google Scholar 

  55. Adachi, M., Suematsu, S., Kondo, T., et al. (1995) Targeted mutation in the Fas gene causes hyperplasia in peripheral lymphoid organs and liver. Nat. Genet. 11, 294–300.

    Article  PubMed  CAS  Google Scholar 

  56. Adachi, M., Suematsu, S., Suda, T., et al. (1996) Enhanced and accelerated lymphoproliferation in Fas-null mice. Proc. Natl. Acad. Sci. USA 93, 2131–2136.

    Article  PubMed  CAS  Google Scholar 

  57. Chervonsky, A. V., Wang, Y., Wong, F. S., et al. (1997) The role of Fas in autoimmune diabetes. Cell 89, 17–24.

    Article  PubMed  CAS  Google Scholar 

  58. Davidson, W. F., Giese, T., and Fredrickson, T. N. (1998) Spontaneous development of plasmacytoid tumors in mice with defective Fas-Fas ligand interactions. J. Exp. Med. 187, 1825–1838.

    Article  PubMed  CAS  Google Scholar 

  59. Chen, A. I., McAdam, A. J., Buhlmann, J. E., et al. (1999) Ox40-ligand has a critical costimulatory role in dendritic cell: T cell interactions. Immunity 11, 689–698.

    Article  PubMed  CAS  Google Scholar 

  60. Akiba, H., Miyahira, Y., Atsuta, M., et al. (2000) Critical contribution of OX40 ligand to T helper cell type 2 differentiation in experimental leishmaniasis. J. Exp. Med. 191, 375–380.

    Article  PubMed  CAS  Google Scholar 

  61. Jember, A. G., Zuberi, R., Liu, F. T., and Croft, M. (2001) Development of allergic inflammation in a murine model of asthma is dependent on the costimulatory receptor OX40. J. Exp. Med. 193, 387–392.

    Article  PubMed  CAS  Google Scholar 

  62. Kopf, M., Ruedl, C., Schmitz, N., et al. (1999) OX40-deficient mice are defective in Th cell proliferation but are competent in generating B cell and CTL responses after virus infection. Immunity 11, 699–708.

    Article  PubMed  CAS  Google Scholar 

  63. Amakawa, R., Hakem, A., Kundig, T. M., et al. (1996) Impaired negative selection of T cells in Hodgkin’s disease antigen CD30-deficient mice. Cell 84, 551–562.

    Article  PubMed  CAS  Google Scholar 

  64. DeYoung, A. L., Duramad, 0., and Winoto, A. (2000) The TNF receptor family member CD30 is not essential for negative selection. J. Immunol. 165, 6170–6173.

    PubMed  CAS  Google Scholar 

  65. Kurts, C., Carbone, F. R., Krummel, M. F., Koch, K. M., Miller, J. F., and Heath, W. R. (1999) Signalling through CD30 protects against autoimmune diabetes mediated by CD8 T cells. Nature 398, 341–344.

    Article  PubMed  CAS  Google Scholar 

  66. Hendriks, J., Gravestein, L. A., Tesselaar, K., van Lier, R. A., Schumacher, T. N., and Borst, J. (2000) CD27 is required for generation and long-term maintenance of T cell immunity. Nat. Immunol. 1, 433–440.

    Article  PubMed  CAS  Google Scholar 

  67. Thompson, J. S., Bixler, S. A., Qian, F., et al. (2001) BAFF-R, a newly identified TNF receptor that specifically interacts with BAFF. Science 293, 2108–2111.

    Article  PubMed  CAS  Google Scholar 

  68. Schiemann, B., Gommerman, J. L., Vora, K., et al. (2001) An essential role for BAFF in the normal development of B cells through a BCMA-independent pathway. Science 293, 2111–2114.

    Article  PubMed  CAS  Google Scholar 

  69. Yan, M., Brady, J. R., Chan, B., et al. (2001) Identification of a novel receptor for B lymphocyte stimulator that is mutated in a mouse strain with severe B cell deficiency. Curr. Biol. 11, 1547–1552.

    Article  PubMed  CAS  Google Scholar 

  70. Xu, S. and Lam, K. P. (2001) B-cell maturation protein, which binds the tumor necrosis factor family members BAFF and APRIL, is dispensable for humoral immune responses. Mol. Cell. Biol. 21, 4067–4074.

    Article  PubMed  CAS  Google Scholar 

  71. Mackay, F. and Browning, J. L. (2002) BAFF: a fundamental survival factor for B cells. Nat. Rev. Immunol. 2, 465–475.

    Article  PubMed  CAS  Google Scholar 

  72. Yan, M., Marsters, S. A., Grewal, I. S., Wang, H., Ashkenazi, A., and Dixit, V. M. (2000) Identification of a receptor for BLyS demonstrates a crucial role in humoral immunity. Nat. Immunol. 1, 37–41.

    Article  PubMed  CAS  Google Scholar 

  73. Yan, M., Wang, H., Chan, B., et al. (2001) Activation and accumulation of B cells in TACI-deficient mice. Nat. Immunol. 2, 638–643.

    Article  PubMed  CAS  Google Scholar 

  74. Schneider, P., Takatsuka, H., Wilson, A., et al. (2001) Maturation of marginal zone and follicular B cells requires B cell activating factor of the tumor necrosis factor family and is independent of B cell maturation antigen. J. Exp. Med. 194, 1691–1697.

    Article  PubMed  CAS  Google Scholar 

  75. von Bulow, G. U., van Deursen, J. M., and Bram, R. J. (2001) Regulation of the T-independent humoral response by TACI. Immunity 14, 573–582.

    Article  Google Scholar 

  76. DeBenedette, M. A., Wen, T., Bachmann, M. F., et al. (1999) Analysis of 4–1BB ligand (4–1BBL)deficient mice and of mice lacking both 4–1BBL and CD28 reveals a role for 4–1BBL in skin allograft rejection and in the cytotoxic T cell response to influenza virus. J. Immunol. 163, 48334841.

    Google Scholar 

  77. Kwon, B. S., Hurtado, J. C., Lee, Z. H., et al. (2002) Immune responses in 4–1BB (CD137)-deficient mice. J. Immunol. 168, 5483–5490.

    PubMed  CAS  Google Scholar 

  78. Tamada, K., Ni, J., Zhu, G., et al. (2002) Cutting edge: selective impairment of CD8+ T cell function in mice lacking the TNF superfamily member LIGHT. J. Immunol. 168, 4832–4835.

    PubMed  CAS  Google Scholar 

  79. Dougall, W. C., Glaccum, M., Charrier, K., et al. (1999) RANK is essential for osteoclast and lymph node development. Genes Dev. 13, 2412–2424.

    Article  PubMed  CAS  Google Scholar 

  80. Kong, Y. Y., Yoshida, H., Sarosi, I., et al. (1999) OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature 397, 315–323.

    Article  PubMed  CAS  Google Scholar 

  81. Fata, J. E., Kong, Y. Y., Li, J., et al. (2000) The osteoclast differentiation factor osteoprotegerinligand is essential for mammary gland development. Cell 103, 41–50.

    Article  PubMed  CAS  Google Scholar 

  82. Cretney, E., Takeda, K., Yagita, H., Glaccum, M., Peschon, J. J., and Smyth, M. J. (2002) Increased susceptibility to tumor initiation and metastasis in TNF-related apoptosis-inducing ligand-deficient mice. J. Immunol. 168, 1356–1361.

    PubMed  CAS  Google Scholar 

  83. Ashkenazi, A. and Dixit, V. M. (1999) Apoptosis control by death and decoy receptors. Curr. Opin. Cell Biol. 11, 255–260.

    Article  PubMed  CAS  Google Scholar 

  84. Sedger, L. M., Glaccum, M. B., Schuh, J. C., et al. (2002) Characterization of the in vivo function of TNF-alpha-related apoptosis-inducing ligand, TRAIL/Apo2L, using TRAIL/Apo2L gene-deficient mice. Eur. J. Immunol. 32, 2246–2254.

    Article  PubMed  CAS  Google Scholar 

  85. Lamhamedi-Cherradi, S. E., Zheng, S. J., Maguschak, K. A., Peschon, J., and Chen, Y. H. (2003) Defective thymocyte apoptosis and accelerated autoimmune diseases in TRAIL(—/—) mice. Nat. Immunol. 4, 255–260.

    Article  PubMed  CAS  Google Scholar 

  86. Ronchetti, S., Nocentini, G., Riccardi, C., and Pandolfi, P. P. (2002) Role of GITR in activation response of T lymphocytes. Blood 100, 350–352.

    Article  PubMed  CAS  Google Scholar 

  87. Srivastava, A. K., Pispa, J., Hartung, A. J., et al. (1997) The Tabby phenotype is caused by mutation in a mouse homologue of the EDA gene that reveals novel mouse and human exons and encodes a protein (ectodysplasin-A) with collagenous domains. Proc. Natl. Acad. Sci. USA 94, 13069–13074.

    Article  PubMed  CAS  Google Scholar 

  88. Tucker, A. S., Headon, D. J., Schneider, P., et al. (2000) Edar/Eda interactions regulate enamel knot formation in tooth morphogenesis. Development 127, 4691–4700.

    PubMed  CAS  Google Scholar 

  89. Koppinen, P., Pispa, J., Laurikkala, J., Thesleff, I., and Mikkola, M. L. (2001) Signaling and sub-cellular localization of the TNF receptor Edar. Exp. Cell. Res. 269, 180–192.

    Article  PubMed  CAS  Google Scholar 

  90. Yan, M., Zhang, Z., Brady, J. R., Schilbach, S., Fairbrother, W. J., and Dixit, V. M. (2002) Identification of a novel death domain-containing adaptor molecule for ectodysplasin-A receptor that is mutated in crinkled mice. Curr. Biol. 12, 409–413.

    Article  PubMed  CAS  Google Scholar 

  91. Naumann, T., Casademunt, E., Hollerbach, E., et al. (2002) Complete deletion of the neurotrophin receptor p75NTR leads to long-lasting increases in the number of basal forebrain cholinergic neurons. J. Neurosci. 22, 2409–2418.

    PubMed  CAS  Google Scholar 

  92. Kindler, V., Sappino, A. P., Grau, G. E., Piguet, P. F., and Vassalli, P. (1989) The inducing role of tumor necrosis factor in the development of bactericidal granulomas during BCG infection. Cell 56, 731–740.

    Article  PubMed  CAS  Google Scholar 

  93. Flynn, J. L. and Chan, J. (2001) Immunology of tuberculosis. Annu. Rev. Immunol. 19, 93–129.

    Article  PubMed  CAS  Google Scholar 

  94. Flynn, J. L., Goldstein, M. M., Chan, J., et al. (1995) Tumor necrosis factor-alpha is required in the protective immune response against Mycobacterium tuberculosis in mice. Immunity 2, 561–572.

    Article  PubMed  CAS  Google Scholar 

  95. Tsenova, L., Bergtold, A., Freedman, V. H., Young, R. A., and Kaplan, G. (1999) Tumor necrosis factor alpha is a determinant of pathogenesis and disease progression in mycobacterial infection in the central nervous system. Proc. Natl. Acad. Sci. USA 96, 5657–5662.

    Article  PubMed  CAS  Google Scholar 

  96. Wilhelm, P., Ritter, U., Labbow, S., et al. (2001) Rapidly fatal leishmaniasis in resistant C57BL/6 mice lacking TNF. J. Immunol. 166, 4012–4019.

    PubMed  CAS  Google Scholar 

  97. Ehlers, S., Benini, J., Kutsch, S., Endres, R., Rietschel, E. T., and Pfeffer, K. (1999) Fatal granuloma necrosis without exacerbated mycobacterial growth in tumor necrosis factor receptor p55 gene-deficient mice intravenously infected with Mycobacterium avium. Infect. Immun. 67, 35713579.

    Google Scholar 

  98. Hultgren, O., Eugster, H. P., Sedgwick, J. D., Korner, H., and Tarkowski, A. (1998) TNF/lymphotoxin-alpha double-mutant mice resist septic arthritis but display increased mortality in response to Staphylococcus aureus..1. Immunol. 161, 5937–5942.

    CAS  Google Scholar 

  99. Grau, G. E., Fajardo, L. F., Piguet, P. F., Allet, B., Lambert, P. H., and Vassalli, P. (1987) Tumor necrosis factor (cachectin) as an essential mediator in murine cerebral malaria. Science 237, 1210–1212.

    Article  PubMed  CAS  Google Scholar 

  100. Rudin, W., Eugster, H. P., Bordmann, G., et al. (1997) Resistance to cerebral malaria in tumor necrosis factor-alpha/beta-deficient mice is associated with a reduction of intercellular adhesion molecule-1 up-regulation and T helper type 1 response. Am. J. Pathol. 150, 257–266.

    PubMed  CAS  Google Scholar 

  101. Li, C. and Langhorne, J. (2000) Tumor necrosis factor alpha p55 receptor is important for development of memory responses to blood-stage malaria infection. Infect. Immun. 68, 5724–5730.

    Article  PubMed  CAS  Google Scholar 

  102. Senaldi, G., Yin, S., Shaklee, C. L., Piguet, P. F., Mak, T. W., and Ulich, T. R. (1996) Corynebacterium parvum-and Mycobacterium bovis bacillus Calmette-Guérin-induced granuloma formation is inhibited in TNF receptor I (TNF-RI) knockout mice and by treatment with soluble TNF-RI. J. Immunol. 157, 5022–5026.

    CAS  Google Scholar 

  103. Kusters, S., Tiegs, G., Alexopoulou, L., et al. (1997) In vivo evidence for a functional role of both tumor necrosis factor (TNF) receptors and transmembrane TNF in experimental hepatitis. Eur. J. Immunol. 27, 2870–2875.

    Article  PubMed  CAS  Google Scholar 

  104. Olleros, M. L., Guler, R., Corazza, N., et al. (2002) Transmembrane TNF induces an efficient cell-mediated immunity and resistance to Mycobacterium bovis bacillus Calmette-Guérin infection in the absence of secreted TNF and lymphotoxin-alpha. J. Immunol. 168, 3394–3401.

    PubMed  CAS  Google Scholar 

  105. Roach, D. R., Briscoe, H., Saunders, B., France, M. P., Riminton, S., and Britton, W. J. (2001) Secreted lymphotoxin-alpha is essential for the control of an intracellular bacterial infection../. Exp. Med. 193, 239–246.

    Article  CAS  Google Scholar 

  106. Engwerda, C. R., Mynott, T. L., Sawhney, S., de Souza, J. B., Bickle, Q. D., and Kaye, P. (2002) Locally up-regulated lymphotoxin-alpha, not systemic tumor necrosis factor-alpha, is the principle mediator of murine cerebral malaria. J. Exp. Med. 195, 1371–1377.

    Article  PubMed  CAS  Google Scholar 

  107. Suresh, M., Lanier, G., Large, M. K., et al. (2002) Role of lymphotoxin alpha in T-cell responses during an acute viral infection. J. Virol. 76, 3943–3951.

    Article  PubMed  CAS  Google Scholar 

  108. Benedict, C. A., Banks, T. A., Senderowicz, L., et al. (2001) Lymphotoxins and cytomegalovirus cooperatively induce interferon-beta, establishing host-virus detente. Immunity 15, 617–626.

    Article  PubMed  CAS  Google Scholar 

  109. Trueb, R., Brown, G., van Huffel, C., Poltorak, A., Valdez-Silva, M., and Beutler, B. (1995) Expression of an adenovirally encoded lymphotoxin-beta inhibitor prevents clearance of Listeria monocytogenes in mice. J. Inflamm. 45, 239–247.

    PubMed  CAS  Google Scholar 

  110. Berger, D. P., Naniche, D., Crowley, M. T., Koni, P. A., Flavell, R. A., and Oldstone, M. B. (1999) Lymphotoxin-beta-deficient mice show defective antiviral immunity. Virology 260, 136–147.

    Article  PubMed  CAS  Google Scholar 

  111. Soong, L., Xu, J. C., Grewal, I. S., et al. (1996) Disruption of CD40–CD40 ligand interactions results in an enhanced susceptibility to Leishmania amazonensis infection. Immunity 4, 263–273.

    Article  PubMed  CAS  Google Scholar 

  112. Campbell, K. A., Ovendale, P. J., Kennedy, M. K., Fanslow, W. C., Reed, S. G., and Maliszewski, C. R. (1996) CD40 ligand is required for protective cell-mediated immunity to Leishmania major. Immunity 4, 283–289.

    Article  CAS  Google Scholar 

  113. Kamanaka, M., Yu, P., Yasui, T., et al. (1996) Protective role of CD40 in Leishmania major infection at two distinct phases of cell-mediated immunity. Immunity 4, 275–281.

    Article  PubMed  CAS  Google Scholar 

  114. Piguet, P. F., Kan, C. D., Vesin, C., Rochat, A., Donati, Y., and Barazzone, C. (2001) Role of CD40CVD4OL in mouse severe malaria. Am. J. Pathol. 159, 733–742.

    Article  PubMed  CAS  Google Scholar 

  115. Andreasen, S. O., Christensen, J. E., Marker, O., and Thomsen, A. R. (2000) Role of CD40 ligand and CD28 in induction and maintenance of antiviral CD8+ effector T cell responses. J. Immunol. 164, 3689–3697.

    PubMed  CAS  Google Scholar 

  116. Whitmire, J. K., Flavell, R. A., Grewal, I. S., Larsen, C. P., Pearson, T. C., and Ahmed, R. (1999) CD40–CD40 ligand costimulation is required for generating antiviral CD4 T cell responses but is dispensable for CD8 T cell responses. J. Immunol. 163, 3194–3201.

    PubMed  CAS  Google Scholar 

  117. Thomsen, A. R., Nansen, A., Christensen, J. P., Andreasen, S. O., and Marker, O. (1998) CD40 ligand is pivotal to efficient control of virus replication in mice infected with lymphocytic choriomeningitis virus. J. Immunol. 161, 4583–4590.

    PubMed  CAS  Google Scholar 

  118. Hotchkiss, R. S., Dunne, W. M., Swanson, P. E., et al. (2001) Role of apoptosis in Pseudomonas aeruginosa pneumonia. Science 294, 1783–1783a.

    Article  PubMed  CAS  Google Scholar 

  119. Grassme, H., Kirschnek, S., Riethmueller, J., et al. (2000) CD95/CD95 ligand interactions on epithelial cells in host defense to Pseudomonas aeruginosa. Science 290, 527–530.

    CAS  Google Scholar 

  120. Jones, N. L., Day, A. S., Jennings, H., Shannon, P. T., Galindo-Mata, E., and Sherman, P. M. (2002) Enhanced disease severity in Helicobacter pylori-infected mice deficient in Fas signaling. Infect. Immun. 70, 2591–2597.

    Article  PubMed  CAS  Google Scholar 

  121. Jensen, E. R., Glass, A. A., Clark, W. R., Wing, E. J., Miller, J. F., and Gregory, S. H. (1998) Fas (CD95)-dependent cell-mediated immunity to Listeria monocytogenes. Infect. Immun. 66, 4143–4150.

    CAS  Google Scholar 

  122. Baran, J., Weglarczyk, K., Mysiak, M., et al. (2001) Fas (CD95)-Fas ligand interactions are responsible for monocyte apoptosis occurring as a result of phagocytosis and killing of Staphylococcus aureus. Infect. Immun. 69, 1287–1297.

    Article  CAS  Google Scholar 

  123. Garcia, I., Miyazaki, Y., Araki, K., et al. (1995) Transgenic mice expressing high levels of soluble TNF-R 1 fusion protein are protected from lethal septic shock and cerebral malaria, and are highly sensitive to Listeria monocytogenes and Leishmania major infections. Eur. J. Immunol. 25, 2401–2407.

    Article  PubMed  CAS  Google Scholar 

  124. Garcia, I., Miyazaki, Y., Marchal, G., Lesslauer, W., and Vassalli, P. (1997) High sensitivity of transgenic mice expressing soluble TNFR1 fusion protein to mycobacterial infections: synergistic action of TNF and IFN-gamma in the differentiation of protective granulomas. Eur. J. Immunol. 27, 3182–3190.

    Article  PubMed  CAS  Google Scholar 

  125. Adams, L. B., Mason, C. M., Kolls, J. K., Scollard, D., Krahenbuhl, J. L., and Nelson, S. (1995) Exacerbation of acute and chronic murine tuberculosis by administration of a tumor necrosis factor receptor-expressing adenovirus. J. Infect. Dis. 171, 400–405.

    Article  PubMed  CAS  Google Scholar 

  126. Jacobs, M., Brown, N., Allie, N., and Ryffel, B. (2000) Fatal Mycobacterium bovis BCG infection in TNF-LT-alpha-deficient mice. Clin. Immunol. 94, 192–199.

    Article  PubMed  CAS  Google Scholar 

  127. Bean, A. G., Roach, D. R., Briscoe, H., et al. (1999) Structural deficiencies in granuloma formation in TNF gene-targeted mice underlie the heightened susceptibility to aerosol Mycobacterium tuberculosis infection, which is not compensated for by lymphotoxin. J. Immunol. 162, 3504–3511.

    PubMed  CAS  Google Scholar 

  128. Bopst, M., Garcia, I., Guler, R., et al. (2001) Differential effects of TNF and LTalpha in the host defense against M. bovis BCG. Eur. J. Immunol. 31, 1935–1943.

    Article  PubMed  CAS  Google Scholar 

  129. Neumann, B., Machleidt, T., Lifka, A., et al. (1996) Crucial role of 55-kilodalton TNF receptor in TNF-induced adhesion molecule expression and leukocyte organ infiltration. J. Immunol. 156, 1587–1593.

    PubMed  CAS  Google Scholar 

  130. Murray, H. W., Jungbluth, A., Ritter, E., Montelibano, C., and Marino, M. W. (2000) Visceral leishmaniasis in mice devoid of tumor necrosis factor and response to treatment. Infect. Immun. 68, 6289–6293.

    Article  PubMed  CAS  Google Scholar 

  131. Nashleanas, M., Kanaly, S., and Scott, P. (1998) Control of Leishmania major infection in mice lacking TNF receptors. J. Immunol. 160, 5506–5513.

    PubMed  CAS  Google Scholar 

  132. You, L. R., Chen, C. M., and Lee, Y. H. W. (1999) Hepatitis C virus core protein enhances NFkappaB signal pathway triggering by lymphotoxin-beta receptor ligand and tumor necrosis factor alpha. J. Virol. 73, 1672–1681.

    PubMed  CAS  Google Scholar 

  133. Magez, S., Radwanska, M., Beschin, A., Sekikawa, K., and de Baetselier, P. (1999) Tumor necrosis factor alpha is a key mediator in the regulation of experimental Trypanosoma brucei infections. Infect. Immun. 67, 3128–3132.

    PubMed  CAS  Google Scholar 

  134. Hodge-Dufour, J., Marino, M. W., Horton, M. R., et al. (1998) Inhibition of interferon gamma induced interleukin 12 production: a potential mechanism for the anti-inflammatory activities of tumor necrosis factor. Proc. Natl. Acad. Sci. USA 95, 13806–13811.

    Article  PubMed  CAS  Google Scholar 

  135. Haas, E., Grell, M., Wajant, H., and Scheurich, P. (1999) Continuous autotropic signaling by membrane-expressed tumor necrosis factor. J. Biol. Chem. 274, 18107–18112.

    Article  PubMed  CAS  Google Scholar 

  136. Kratz, A., Campos-Neto, A., Hanson, M. S., and Ruddle, N. H. (1996) Chronic inflammation caused by lymphotoxin is lymphoid neogenesis. J. Exp. Med. 183, 1461–1472.

    Article  PubMed  CAS  Google Scholar 

  137. Sacca, R., Cuff, C. A., Lesslauer, W., and Ruddle, N. H. (1998) Differential activities of secreted lymphotoxin-alpha3 and membrane lymphotoxin-alphalbeta2 in lymphotoxin-induced inflammation: critical role of TNF receptor 1 signaling. J. Immunol. 160, 485–491.

    PubMed  CAS  Google Scholar 

  138. Cuff, C. A., Schwartz, J., Bergman, C. M., Russell, K. S., Bender, J. R., and Ruddle, N. H. (1998) Lymphotoxin alpha3 induces chemokines and adhesion molecules: insight into the role of LT alpha in inflammation and lymphoid organ development. J. Immunol. 161, 6853–6860.

    PubMed  CAS  Google Scholar 

  139. Netea, M. G., van Tits, L. J., Curfs, J. H., et al. (1999) Increased susceptibility of TNF-alpha lymphotoxin-alpha double knockout mice to systemic candidiasis through impaired recruitment of neutrophils and phagocytosis of Candida albicans. J. Immunol. 163, 1498–1505.

    CAS  Google Scholar 

  140. Lucas, R., Tacchini-Cottier, F., Guler, R., et al. (1999) A role for lymphotoxin beta receptor in host defense against Mycobacterium bovis BCG infection. Eur. J. Immunol. 29, 4002–4010.

    Article  PubMed  CAS  Google Scholar 

  141. Montrasio, F., Frigg, R., Glatzel, M., et al. (2000) Impaired prion replication in spleens of mice lacking functional follicular dendritic cells. Science 288, 1257–1259.

    Article  PubMed  CAS  Google Scholar 

  142. Prinz, M., Montrasio, F., Klein, M. A., et al. (2002) Lymph nodal prion replication and neuro-invasion in mice devoid of follicular dendritic cells. Proc. Natl. Acad. Sci. USA 99, 919–924.

    Article  PubMed  CAS  Google Scholar 

  143. Ndhlovu, L. C., Ishii, N., Murata, K., Sato, T., and Sugamura, K. (2001) Critical involvement of OX40 ligand signals in the T cell priming events during experimental autoimmune encephalomyelitis. J. Immunol. 167, 2991–2999.

    PubMed  CAS  Google Scholar 

  144. Litinskiy, M. B., Nardelli, B., Hilbert, D. M., et al. (2002) DCs induce CD40-independent immunoglobulin class switching through BLyS and APRIL. Nat. Immunol. 3, 822–829.

    Article  PubMed  CAS  Google Scholar 

  145. Smyth, M. J., Kelly, J. M., Baxter, A. G., Korner, H., and Sedgwick, J. D. (1998) An essential role for tumor necrosis factor in natural killer cell-mediated tumor rejection in the peritoneum. J. Exp. Med. 188, 1611–1619.

    Article  PubMed  CAS  Google Scholar 

  146. Arnott, C. H., Scott, K. A., Moore, R. J., et al. (2002) Tumour necrosis factor-alpha mediates tumour promotion via a PKC alpha-and AP-1-dependent pathway. Oncogene 21, 4728–4738.

    Article  PubMed  CAS  Google Scholar 

  147. Starcher, B. (2000) Role for tumour necrosis factor-alpha receptors in ultraviolet-induced skin tumours. Br. J. Dermatol. 142, 1140–1147.

    Article  PubMed  CAS  Google Scholar 

  148. Knight, B., Yeoh, G. C., Husk, K. L., et al. (2000) Impaired preneoplastic changes and liver tumor formation in tumor necrosis factor receptor type 1 knockout mice. J. Exp. Med. 192, 1809–1818.

    Article  PubMed  CAS  Google Scholar 

  149. Cohen, P. L. and Eisenberg, R. A. (1991) Lpr and gld: single gene models of systemic autoimmunity and lymphoproliferative disease. Annu. Rev. Immunol. 9, 243–269.

    Article  PubMed  CAS  Google Scholar 

  150. Wigginton, J. M., Gruys, E., Geiselhart, L., et al. (2001) IFN-gamma and Fas/FasL are required for the antitumor and antiangiogenic effects of IL-12/pulse IL-2 therapy. J. Clin. Invest. 108, 51–62.

    PubMed  CAS  Google Scholar 

  151. Hahne, M., Rimoldi, D., Schroter, M., et al. (1996) Melanoma cell expression of Fas(Apo-1/CD95) ligand: implications for tumor immune escape. Science 274, 1363–1366.

    Article  PubMed  CAS  Google Scholar 

  152. Igney, F. H. and Krammer, P. H. (2002) Immune escape of tumors: apoptosis resistance and tumor counterattack. J. Leukoc. Biol. 71, 907–920.

    PubMed  CAS  Google Scholar 

  153. Chappell, D. B., Zaks, T. Z., Rosenberg, S. A., and Restifo, N. P. (1999) Human melanoma cells do not express Fas (Apo-l/CD95) ligand. Cancer Res. 59, 59–62.

    PubMed  CAS  Google Scholar 

  154. Tada, Y., Wang, J., Takiguchi, Y., et al. (2002) Cutting edge: a novel role for Fas ligand in facilitating antigen acquisition by dendritic cells. J. Immunol. 169, 2241–2245.

    PubMed  CAS  Google Scholar 

  155. Ito, D., Back, T. C., Shakhov, A. N., Wiltrout, R. H., and Nedospasov, S. A. (1999) Mice with a targeted mutation in lymphotoxin-alpha exhibit enhanced tumor growth and metastasis: impaired NK cell development and recruitment. J. Immunol. 163, 2809–2815.

    PubMed  CAS  Google Scholar 

  156. Smyth, M. J., Johnstone, R. W., Cretney, E., et al. (1999) Multiple deficiencies underlie NK cell inactivity in lymphotoxin-alpha gene-targeted mice. J. Immunol. 163, 1350–1353.

    PubMed  CAS  Google Scholar 

  157. Iizuka, K., Chaplin, D. D., Wang, Y., et al. (1999) Requirement for membrane lymphotoxin in natural killer cell development. Proc. Natl. Acad. Sci. USA 96, 6336–6340.

    Article  PubMed  CAS  Google Scholar 

  158. Browning, J. L., Miatkowski, K., Sizing, I., et al. (1996) Signaling through the lymphotoxin beta receptor induces the death of some adenocarcinoma tumor lines. J. Exp. Med. 183, 867–878.

    Article  PubMed  CAS  Google Scholar 

  159. Degli-Esposti, M. A., Davis-Smith, T., Din, W. S., Smolak, P. J., Goodwin, R. G., and Smith, C. A. (1997) Activation of the lymphotoxin beta receptor by cross-linking induces chemokine production and growth arrest in A375 melanoma cells. J. Immunol. 158, 1756–1762.

    PubMed  CAS  Google Scholar 

  160. Wu, M. Y., Wang, P. Y., Han, S. H., and Hsieh, S. L. (1999) The cytoplasmic domain of the lymphotoxin-beta receptor mediates cell death in HeLa cells. J. Biol. Chem. 274, 11868–11873.

    Article  PubMed  CAS  Google Scholar 

  161. Rooney, I. A., Butrovich, K. D., Glass, A. A., et al. (2000) The lymphotoxin-beta receptor is necessary and sufficient for LIGHT-mediated apoptosis of tumor cells. J. Biol. Chem. 275, 14307–14315.

    Article  PubMed  CAS  Google Scholar 

  162. Hehlgans, T., Stoelcker, B., Stopfer, P., et al. (2002) Lymphotoxin-beta receptor immune interaction promotes tumor growth by inducing angiogenesis. Cancer Res. 62, 4034–4040.

    PubMed  CAS  Google Scholar 

  163. Takeda, K., Hayakawa, Y., Smyth, M. J., et al. (2001) Involvement of tumor necrosis factor-related apoptosis-inducing ligand in surveillance of tumor metastasis by liver natural killer cells. Nat. Med. 7, 94–100.

    Article  PubMed  CAS  Google Scholar 

  164. Kayagaki, N., Yamaguchi, N., Nakayama, M., et al. (1999) Expression and function of TNFrelated apoptosis-inducing ligand on murine activated NK cells. J. Immunol. 163, 1906–1913.

    PubMed  CAS  Google Scholar 

  165. Sato, K., Hida, S., Takayanagi, H., et al. (2001) Antiviral response by natural killer cells through TRAIL gene induction by IFN-alpha/beta. Eur. J. Immunol. 31, 3138–3146.

    Article  PubMed  CAS  Google Scholar 

  166. Schmaltz, C., Alpdogan, O., Kappel, B. J., et al. (2002) T cells require TRAIL for optimal graft-versustumor activity. Nat. Med. 8, 1433–1437.

    Article  PubMed  CAS  Google Scholar 

  167. Hahne, M., Kataoka, T., Schroter, M., et al. (1998) APRIL, a new ligand of the tumor necrosis factor family, stimulates tumor cell growth. J. Exp. Med. 188, 1185–1190.

    Article  PubMed  CAS  Google Scholar 

  168. Rennert, P., Schneider, P., Cachero, T. G., et al. (2000) A soluble form of B cell maturation antigen, a receptor for the tumor necrosis factor family member APRIL, inhibits tumor cell growth. J. Exp. Med. 192, 1677–1684.

    Article  PubMed  CAS  Google Scholar 

  169. Pearse, R. N., Sordillo, E. M., Yaccoby, S., et al. (2001) Multiple myeloma disrupts the TRANCE/ osteoprotegerin cytokine axis to trigger bone destruction and promote tumor progression. Proc. Natl. Acad. Sci. USA 98, 11581–11586.

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. Sergei A. Nedospasov
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  2. Sergei I. Grivennikov
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  3. Dmitry V. Kuprash
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  1. University of Colorado Health Sciences Center, Denver, CO, USA

    Giamila Fantuzzi PhD

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Nedospasov, S.A., Grivennikov, S.I., Kuprash, D.V. (2003). Physiologic Roles of Members of the TNF and TNF Receptor Families as Revealed by Knockout Models. In: Fantuzzi, G. (eds) Cytokine Knockouts. Contemporary Immunology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-405-4_25

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  • DOI: https://doi.org/10.1007/978-1-59259-405-4_25

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