Abstract
Tumor necrosis factor (TNF) has a long history that goes back well into the last century. It is now a hundred years ago that the surgeon William Coley observed a remission of inoperable tumors in some patients after infusion of bacterial toxins (1,2). Unacceptable side effects, however, and a lack of understanding of how these toxins induced hemorrhages in tumors, prevented the further development and application of this treatment. It was more than 60 years later when O’Malley et al. (3) realized that bacterial toxins acted indirectly by inducing an endogenous factor in the host that caused hemorrhagic necrosis in tumors and was hence later called TNF (4,5).Since then, TNF has attracted a great deal of attention and was found to participate in a vast variety of cellular activities that collectively make it the most pleiotropic cytokine identified so far.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
references
Coley, W. B. (1893) The treatment of malignant tumors by repeated inoculations of erysipelas; with a report of ten original cases. Am. J. Med. Sci. 105, 487–511.
Coley, W. B. (1894) Treatment of inoperable malignant tumors with toxins of erysipelas and the bacillus prodigiosus. Trans. Am. Surg. Assoc. 12, 183–212.
O’Malley, W. E., Achinstein, B., Shear, M. J. (1962) Action of bacterial polysaccharide on tumors. II. Damage of sarcoma 37 by serum of mice treated with Serratia marcescens polysaccharide, and induced tolerance. J. Natl. Cancer. Inst. 29, 1169–1175.
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 175, 3666–3670.
Helson, L., Green, S., Carswell, E., and Old, L. J. (1975) Effect of tumor necrosis factor on cultured human melanoma cells. Nature 258, 731–732.
Smith, C. A., Farrah, T., and Goodwin, R. G. (1994) The TNF receptor super-family of cellular and viral proteins: activation, costimulation, and death. Cell 76, 959–962.
Beutler, B., and van Huffel, C. (1994) Unraveling function in the TNF ligand and receptor families (comment). Science 264, 667–668.
Vandenabeele, P., Declercq, W., Beyaert, R., and Fiers, W. (1995) Two tumour necrosis factor receptors: Structure and function. Trends Cell Biol. 5, 392–399.
Wiley, S. R., Schooley, K., Smolak, P. J., et al. (1995) Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity 3, 673–682.
Engelmann, H., Holtmann, H., Brakebusch, C., Avni, Y. S., Sarov, I., Nophar, Y., Hadas, E., Leitner, O., and Wallach, D. (1990) Antibodies to a soluble form of a tumor necrosis factor (TNF) receptor have TNF-like activity. J. Biol. Chem. 265, 14497–14504.
Itoh, N., Yonehara, S., Ishii, A., Yonehara, M., Mizushima, S., Sameshima, M., Hase, A., Seto, Y., and Nagata, S. (1991) The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis. Cell 66, 233–243.
Tartaglia, L. A., Ayres, T. M., Wong, G. H., and Goeddel, D. V. (1993) A novel domain within the 55 kd TNF receptor signals cell death. Cell 74, 845–53.
Itoh, N., and Nagata, S. (1993) A novel protein domain required for apoptosis. J. Biol. Chem. 268, 10,932–10, 937.
Wong, G. H. and Goeddel, D. V. (1994) Fas antigen and p55 TNF receptor signal apoptosis through distinct pathways. J. Immunol. 152, 1751–1755.
Schulze-Osthoff, K., Krammer, P. H., and Droge, W. (1994) Divergent signalling via APO-1/Fas and the TNF receptor, two homologous molecules involved in physiological cell death. EMBO J. 13, 4587–4596.
Zheng, L., Fisher, G., Miller, R. E., Peschon, J., Lynch, D. H., and Lenardo, M. J. (1995) Induction of apoptosis in mature T cells by tumour necrosis factor. Nature 377, 348–351.
Rousset, F., Garcia, E., and Banchereau, J. (1991) Cytokine-induced proliferation and immunoglobulin production of human B lymphocytes triggered through their CD40 antigen. J. Exp. Med. 173, 705–710.
Liu, Y. J., Mason, D. Y., Johnson, G. D., Abbot, S., Gregory, C. D., Hardie, D. L., Gordon, J., and MacLennan, I. C. (1991) Germinal center cells express
bc1–2 protein after activation by signals which prevent their entry into apoptosis. Eur. J. Immunol. 21, 1905–10.
Kriegler, M., Perez, C., DeFay, K., Albert, L., and Lu, S. D. (1988) A novel form of TNF/cachectin is a cell surface cytotoxin transmembrane protein: ramifications for the complex physiology of TNF. Cell 53, 45–53.
Grell, M., Douni, E., Wajant, H., Lohden, M., Clauss, M., Maxeiner, B., Georgopoulos, S., Lesslauer, W., Kollias, G., Pfizenmaier, K., et al. (1995) The transmembrane form of tumor necrosis factor is the prime activating ligand of the 80 kDa tumor necrosis factor receptor. Cell 83, 793–802.
Mohler, K. M., Sleath, P. R., Fitzner, J. N., Cerretti, D. P., Alderson, M., Kerwar, S. S., Torrance, D. S., Otten Evans, C. Greenstreet, T., Weerawarna, K., et al. (1994) Protection against a lethal dose of endotoxin by an inhibitor of tumour necrosis factor processing. Nature 370, 218–220.
Gearing, A. J. H., Beckett, P., Christodoulou, M., Churchill, M., Clements, J., Davidson, A. H., Drummond, A. H., Galloway, W. A., Gilbert, R., Gordon, J. L., Leber, T. M., Mangan, M., Miller, K., Nayee, P., Owen, K., Patel, S., Thomas, W., Wells, G., Wood, L. M., and Woolley, K. (1994) Processing of tumor necrosis factor-a precursor by metalloproteinases. Nature 370, 555–557.
McGeehan, G. M., Becherer, J. D., Jr. Bast, R. C., Boyer, C. M., Champion, B., Connolly, K. M., Conway, J. G., Furdon, P., Karp, S., Kidao, S., McElroy, A. B., Nichols, J., Pryzwansky, K. M., Schoenen, F., Sekut, L., Truesdale, A., Verghese, M., Warner, J. and Ways, J. P. (1994) Regulation of tumour necrosis factor-alpha processing by a metalloproteinase inhibitor. Nature 370, 558–561.
Loetscher, H., Pan, Y. C., Lahm, H. W., Gentz, R., Brockhaus, M., Tabuchi, H., and Lesslauer, W. (1990) Molecular cloning and expression of the human 55 kd tumor necrosis factor receptor. Cell 61, 351–359.
Schall, T. J., Lewis, M., Koller, K. J., Lee, A., Rice, G. C., Wong, G. H., Gatanaga, T., Granger, G. A., Lentz, R., Raab, H. et al. (1990) Molecular cloning and expression of a receptor for human tumor necrosis factor. Cell 61, 361–370.
Smith, C. A., Davis, T., Anderson, D., Solam, L., Beckmann, M. P., Jerzy, R., Dower, S. K., Cosman, D., and Goodwin, R. G. (1990) A receptor for tumor necrosis factor defines an unusual family of cellular and viral proteins. Science 248, 1019–1023.
Loetscher, H., Stueber, D., Banner, D., Mackay, F., and Lesslauer, W. (1993) Human tumor necrosis factor alpha (TNF alpha) mutants with exclusive specificity for the 55—kDa or 75—kDa TNF receptors. J. Biol. Chem. 268, 26350–26357.
Tartaglia, L. A., Pennica, D., and Goeddel, D. V. (1993) Ligand passing: the 75-kDa tumor necrosis factor (TNF) receptor recruits TNF for signaling by the 55-kDa TNF receptor. J. Biol. Chem. 268, 18,542–18, 548.
Vassalli, P. (1992) The pathophysiology of tumor necrosis factors. Annu. Rev. Immunol. 10, 411–452.
Paul, N. L. and Ruddle, N. H. (1988) Lymphotoxin. Ann. Rev. Immunol. 6, 407–438.
Browning, J. L., Ngam-ek, A., Lawton, P., DeMarinis, J., Tizard, R., Chow, E. P., Hession, C., O’Brine-Greco, B., Foley, S. F., and Ware, C. F. (1993) Lymphotoxin 13, a novel member of the TNF Family that forms a heteromeric complex with Lymphotoxin on the cell surface. Cell 72, 847–856.
Crowe, P. D., VanArsdale, T. L., Walter, B. N., Ware, C. F., Hession, C., Ehrenfels, B., Browning, J., Din, W. S., Goodwin, R. G., and Smith, C. A. (1994) A lymphotoxin-(3—specific receptor. Science 264, 707–710.
De Togni, P., Goellner, J., Ruddle, N. H., Streeter, P. R., Fick, A., Mariathasan, S., Smith, S. C., Carlson, R., Shornick, L. P., Strauss-Schoenberger, J., Russell, J. H., Karr, R., and Chaplin. D. D. (1994) Abnormal development of peripheral lymphoid organs in mice deficient in lymphotoxin (see comments). Science 264, 703–707.
Eugster, H. P., Müller, M., Car, B. D., Karrer, U., Schnyder, B., Eng, V. M., Woerly, G., Aguet, M., Zinkernagel, R., Bluethmann, H., and Ryffel, B. (1996) Multiple immune abnormalities in tumor necrosis factor and lymphotoxin-alpha double-deficient mice. Int. Immunol. 8, 23–36.
Hohmann, H. P., Brockhaus, M., Baeuerle, P., Remy, R., Kolbeck, R., van Loon, A. (1990) Expression of the types A and B tumor necrosi factor (TNF) receptors is independently regulated, and both receptors mediate activation of the transcription factor NF-KB. J. Biol. Chem. 265, 22,409–22, 417.
Rothe, J., Bluethmann, H., Gentz, R., Lesslauer, W., Steinmetz, M. (1993) Genomic organization and promoter function of the murine tumor necrosis factor receptor beta gene. Mol. Immunol. 30, 165–175.
Ohsawa, T. and Natori, S. (1989) Expression of tumor necrosis factor at a specific developmental stage of mouse embryos. Dev. Biol. 135, 459–461.
Hunt, J. S., Chen, H. L., Hu, X. L., Chen, T. Y., and Morrison, D. C. (1992) Tumor necrosis factor-alpha gene expression in the tissues of normal mice. Cytokine 4, 340–346.
Parr, E. L., Chen, H. L., Parr, M. B., and Hunt, J. S. (1995) Synthesis and granular localization of tumor necrosis factor-alpha in activated NK cells in the pregnant mouse uterus. J. Reprod. Immunol. 28, 31–40.
Rothe, J., Lesslauer, W., Lotscher, H., Lang, Y., Koebel, P., Kontgen, F., Althage, A., Zinkernagel, R., Steinmetz, M., and Bluethmann, H (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.
Pfeffer, K., Matsuyama, T., Kundig, T. M., Wakeham, A., Kishihara, K., Shahinian, A., Wiegmann, K., Ohashi, P. S., Krönke, M., and Mak, T. W. (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.
Erickson, S. L., de Sauvage, F. J., Kikly, K., Carver Moore, K., Pitts Meek, S., Gillett, N., Sheehan, K. C., Schreiber, R. D., Goeddel, D. V., and Moore. M. W. (1994) Decreased sensitivity to turnour-necrosis factor but normal T-cell development in TNF receptor-2-deficient mice. Nature 372, 560–563.
Giroir, B. P., Brown, T., and Beutler, B. (1992) Constitutive synthesis of tumor necrosis factor in the thymus. Proc. Natl. Acad. Sci. USA 89, 4864–4868.
de Kossodo, S., Grau, G. E., Daneva, T., Pointaire, P., Fossati, L., Ody, C., Zapf, J., Piguet, P. F., Gaillard, R. C., and Vassalli, P. (1992) Tumor necrosis factor a is involved in mouse growth and lymphoid tissue development. J. Exp. Med. 176, 1259–1264.
Ranges, G. E., Zlotnik, A., Espevik, T., Dinarello, C. A., Cerami, A., Palladino, M. A. J. (1988) Tumor necrosis factor alpha/cachectin is a growth factor for thymocytes. Synergistic interactions with other cytokines. J. Exp. Med. 167, 1472–1478.
Zuniga Pflucker, J. C., Di, J., and Lenardo, M. J. (1995) Requirement for TNF-alpha and IL-1 alpha in fetal thymocyte commitment and differentiation. Science 268, 1906–1909.
Zhang, Y., Harada, A., Bluethmann, H., Wang, J. B., Nakao, S., Mukaida, N., and Matsushima, K. (1995) Tumor necrosis factor (TNF) is a physiologic regulator of hematopoietic progenitor cells: Increase of early hematopoietic progenitor cells in TNF receptor p55-deficient mice in vivo and potent inhibition of progenitor cell proliferation by TNF alpha in vitro. Blood 86, 2930–2937.
Slordal, L., Warren, D. J., and Moore, M. A. (1990) Protective effects of tumor necrosis factor on murine hematopoiesis during cycle-specific cytotoxic chemotherapy. Cancer Res. 50, 4216–4220.
Le Hir, M., Bluethmann, H., Kosco-Vilbois, M. H., Müller, M., di Padova, F., Moore, M., Ryffel, B., and Eugster, H.-P. (1996) Differentiation of follicular dendritic cells (FDC) and full antibody responses require TNF receptor-1 (TNFR1) signalling. J. Exp. Med. 183, 2367–2372.
Matsumoto, M., Marithasan, S., Nahm, M. H., Baranyay, F., Peschon, J. J., Chaplin, D. D. (1996) Role of Lymphotoxin and the type I TNF receptor in the formation of germinal centers. Science 271, 1289–1291.
Müller, M., Eugster, H. P., Le Hir, M., Shakov, A., Di Padova, F., Maurer, C., Quesniaux, V., and Ryffel, B. (1996) Correction or transfer of the TNF/LTadeficient phenotype by bone marrow transplantation. Mol. Med. 2, 247–255.
Nakane, A. (1992) TNF in Listeriosis, in Tumor Necrosis Factor: The Molecules and their Emerging Role in Medicine. ( Beutler B, ed.), Raven, New York, pp. 285–292.
Havell, E. A. (1987) Production of tumor necrosis factor during murine listeriosis. J. Immunol. 139, 4225–4231.
Nakane, A., Minagawa, T., Yasuda, I., Yu, C., and Kato, K. (1988) Prevention by gamma interferon of fatal infection with Listeria monocytogenes in mice treated with cyclosporin A. Infect. Immun. 56, 2011–2015.
Hauser, T., Frei, K., Zinkernagel, R. M., Leist, T. P. (1990) Role of tumor necrosis factor in Listeria resistance of nude mice. Med. Microbiol. Immunol. (Berl) 179, 95–104.
Buchmeier, N. A., and Schreiber, R. D. (1985) Requirement of endogenous interferon-gamma production for resolution of Listeria monocytogenes infection. Proc. Natl. Acad. Sci. USA 82, 7404–7408.
Bancroft, G. J., Schreiber, R. D., Bosma, G. C., Bosma, M. J., and Unanue, E. R. (1987) A T cell-independent mechanism of macrophage activation by interferon-gamma J. Immunol. 139, 1104–1107.
Huang, S., Hendriks, W., Althage, A., Hemmi, S., Bluethmann, H., Kamijo, R., Vilcek, J., Zinkernagel, R. M., and Aguet, M. (1993) Immune response in mice that lack the interferon-gamma receptor (see comments). Science 259, 1742–1745.
Flynn, J. L., Goldstein, M. M., Chan, J., Triebold, K. J., Pfeffer, K., Lowenstein, C. J., Schreiber, R., Mak, T. W., and Bloom, B. R. (1995) Tumor necrosis factor-alpha is required in the protective immune response against Mycobacterium tuberculosis in mice. Immunity 2, 561–572.
Kamijo, R., Le, J., Shapiro, D., Havell, E. A., Huang, S., Aguet, M., Bosland, M., and Vilcek, J. (1993) Mice that lack the interferon-y receptor have profoundly altered responses to infection with Bacillus Calmette-Guerin and subsequent challenge with lipopolysaccharide. J. Exp. Med. 178, 1435–40.
Alexander, J., Jebbari, H., Bluethmann, H., Satoskar, A., and Roberts, C. W. (1996) Immunological control of Toxoplasma gondii and appropriate vaccine design. Curr. Topics Immunol. Microbiol. 219, 183–195.
Nussler, A. K., and Billiar, T. R. (1993) InfJlammation, immunoregulation, and inducible nitric oxide synthetase. J. Leukoc. Biol. 54, 171–178.
Bluethmann, H., Rothe, J., Schultze, N., Tkachuk, M., and Koebel, P. (1994) Establishment of the role of IL-6 and TNF receptor 1 using gene knockout mice. J. Leukoc. Biol. 56, 565–570.
Kamijo, R., Shapiro, D., Le, J., Huang, S., Aguet, M., and Vilcek, J. (1993) Generation of nitric oxide and induction of major histocompatibility complex class II antigen in macrophages from mice lacking the interferon y receptor. Proc. Natl. Acad. Sci. USA 90, 6626–6630.
Trinchieri, G. (1995) Interleukin-12: a proinflammatory cytokine with immunoregulatory functions that bridge innate resistance and antigen-specific adaptive immunity. Annu. Rev. Immunol. 13, 251–276.
D Andrea, A., Rengaraju, M., Valiante, N. M., Chehimi, J., Kubin, M., Aste, M., Chan, S. H., Kobayashi, M., Young, D., Nickbarg, E., et al. (1992) Production of natural killer cell stimulatory factor (interleukin 12) by peripheral blood mononuclear cells. J. Exp. Med. 176, 1387–1398.
Chan, S. H., Perussia, B., Gupta, J. W., Kobayashi, M., Pospisil, M., Young, H. A., Wolf, S. F., Young, D., Clark, S. C., and Trinchieri, G. (1991) Induction of interferon gamma production by natural killer cell stimulatory factor: characterization of the responder cells and synergy with other inducers. J. Exp. Med. 173, 869–879.
Gazzinelli, R. T., Hieny, S., Wynn, T., Wolf. S., and Sher, A. (1993) IL-12 is required for the T-cell independent induction of IFN-y by an intracellular parasite and induces resistance in T-deficient hosts. Proc. Natl. Acad. Sci. USA 90, 6115–6119.
Tripp, C. S., Gately, M. K., Hakimi, J., Ling, P., and Unanue, E. R. (1994) Neutralization of IL-12 decreases resistance. to Listeria in SCID and C.B-17 mice. Reversal by IFN-gamma. J. Immunol. 152, 1883–1887.
Farrar, M. A., and Schreiber, R. D. (1993) The molecular cell biology of interferon-y and its receptor. Annu. Rev. Immunol. 11, 571–611.
Beutler, B., Milsark, I. W., and Cerami, A. C. (1985) Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin. Science 229, 869–871.
Tracey, K. J., Beutler, B., Lowry, S.F., Merryweather, J., Wolpe, S., Milsark, I. W., Hariri, R. J., Fahey, T. J., Zentella, A., Albert, J. D., Shires, G. T., and Cerami, A. (1986) Shock and tissue injury induced by recompinant human cachectin. Science 234, 470–474.
Morrison, D. C., and Ryan, J. L. (1987) Endotoxin and disease mechanisms. Annu. Rev. Med. 38, 417–432.
Miethke, T., Wahl, C., Heeg, K., Echtenacher, B., Krammer, P. H., and Wagner, H. (1992) T cell-mediated lethal shock triggered in mice by the superantigen staphylococcal enterotoxin B: critical role of tumor necrosis factor. J. Exp. Med. 175, 91–98.
Waage, A., and Espevik, T. (1988) Interleukin 1 potentiates the lethal effect of tumor necrosis factor alpha/cachectin in mice. J. Exp. Med. 167, 1987–1992.
Galanos, C., Freudenberg, M. A., and Reutter, W. (1979) Galactosamineinduced sensitisation to the lethal effects of endotoxin. Proc. Natl. Acad. Sci. USA 76, 5939–5943.
Tiegs, G., Wolter, M., and Wendel, A. (1989) Tumor necrosis factor is a terminal mediator in galactosamine/endotoxin-induced hepatitis in mice. Biochem. Pharmacol. 38, 627–631.
Bahrami, S., Redl, H., Leichtfeld, G., Yu, Y., and Schlag, G. (1994) Similar cytokine but different coagulation responses to lipopolysaccharide injection in D-galactosamine-sensitized vs nonsensitized rats. Infect. Immunol. 62, 99.
Decker, K. and Keppler, D. (1974) Galactosamine hepatitis: key role of the nucleotide deficiency period in the pathogenesis of cell injury and cell death. Rev. Physiol. Biochem. Pharmacol. 71, 77.
Leist, M., Gantner, F., Bohlinger, I., Germann, P. G., Tiegs, G. and Wendel, A. (1994) Murine hepatocyte apoptosis induced in vitro and in vivo by TNFalpha requires transcriptional arrest. J. Immunol. 153, 1778–1788.
Leist, M., Gantner, F., Jilg, S., and Wendel, A. (1995) Activation of the 55 kDa TNF receptor is necessary and sufficient for TNF-induced liver failure, hepatocyte apoptosis, and nitrite release. J. Immunol. 154, 1307–1316.
Li, P., Allen, H., Banerjee, S., Franklin, S., Herzog, L., Johnston, C., McDowell, J., Paskind, M., Rodman, L., Salfeld, J. et al. (1995) Mice deficient in IL-1 beta-converting enzyme are defective in production of mature IL-1 beta and resistant to endotoxic shock. Cell 80, 401–411.
Xu, H., Gonzalo, J. A., St Pierre, Y., Williams, I. R., Kupper, T. S., Cotran, R. S., Springer, T. A., and Gutierrez Ramos, J. C. (1994) Leukocytosis and resistance to septic shock in intercellular adhesion molecule 1-deficient mice. J. Exp. Med. 180, 95–109.
Tartaglia, L. A., Rothe, M., Hu, Y. F., and Goeddel, D. V. (1993) Tumor necrosis factor’s cytotoxic activity is signaled by the p55 TNF receptor. Cell 73, 213–216.
Leist, M., Gantner, F., Künstle, G., Bohlinger, I., Tiegs, G., Bluethmann, H., and Wendel, A. (1996) The 55 kDa tumor necrosis factor receptor and CD95 (fas) independently signal murine hepatocyte apoptosis and subsequent liver failure. Mol. Med. 2, 109–124.
Zhou, T., Edwards, C. K., Yang, P., Wang, Z., Bluethmann, H., and Mountz, J. D. (1996) Greatly accelerated lymphadenopathy and autoimmune disease in 1pr mice lacking tumor necrosis factor receptor 1. J. Immunol. 156, 2661–2665.
Jacob, C. 0. (1992) Studies on the role of tumor necrosis factor in murine and human autoimmunity. J. Autoimmun. 5 (Suppll A), 133–143.
Feldmann, M., Brennan, F. M., Williams, R. O., Cope, A. P., Gibbons, D. L., Katsikis, P. D., and Maini, R. N. (1992) Evaluation of the role of cytokines in autoimmune disease: the importance of TNF alpha in rheumatoid arthritis. Prog. Growth Factor Res. 4, 247–55.
Tartaglia, L. A., Goeddel, D. V. (1992) Two T’NF receptors. Immunol. Today 13, 151–153.
Rothe, M., Wong, S. C., Henzel, W. J., and Goeddel, D. V. (1994) A novel family of putative signal transducers associated with the cytoplasmic domain of the 75 kDa tumor necrosis factor receptor. Cell 78, 681–692.
Hsu, H., Xiong, J., Goeddel, D. V. (1995) The TNF receptor 1-associated protein TRADD signals cell death and NF-kappa B activation. Cell 81, 495–504.
Hsu, H. L., Shu, H. B., Pan, M. G., and Goeddel, D. V. (1996) TRADDTRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways. Cell 84, 299–308.
Decoster, E., Vanhaesebroeck, B., Vandenabeele, P., Grooten, J., and Fiers, W. (1995) Generation and biological characterization of membrane-bound, uncleavable murine tumor necrosis factor. J. Biol. Chem. 270, 18473–18478.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1998 Springer Science+Business Media New York
About this chapter
Cite this chapter
Bluethmann, H. (1998). Physiological, Immunological, and Pathological Functions of Tumor Necrosis Factor (TNF) Revealed by TNF Receptor-Deficient Mice. In: Durum, S.K., Muegge, K. (eds) Cytokine Knockouts. Contemporary Immunology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-4757-2753-1_5
Download citation
DOI: https://doi.org/10.1007/978-1-4757-2753-1_5
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-4757-2755-5
Online ISBN: 978-1-4757-2753-1
eBook Packages: Springer Book Archive