Abstract
Tumour necrosis factor and lymphotoxin-α (TNF and LTα) are multipotent cytokines showing a wide range of activities that extend beyond their well characterised pleiotropic proinflammatory properties to include diverse signals for cellular differentiation, proliferation and death. TNF is produced in response to various stimuli mainly by macrophages and T cells and is shown to be bioactive both as a transmembrane protein and as a homotrimeric secreted molecule (Vasali, 1992; Kriegler et al, 1988). LTα, originally identified as a major product of lymphocytes, exists as a secreted molecule only in a homotrimeric form (Paul and Ruddle, 1988), but it may also accumulate on the cellular membrane of lymphocytes when complexed with LTβ, a type II transmembrane protein that is another member of the TNF ligand family (Browning et al, 1993). LTα1β2 trimers signal exclusively through the LTα receptor(s) (Crowe et al, 1994), while TNFα and LTα share the same cell surface receptors, designated p55 and p75 TNF-R, which show common but also differential activities depending on the cell type in which they operate (Vandenabeele et al, 1995). p75 TNF-R signalling has been mainly implicated in lymphocyte proliferation (Espevik et al, 1990; Tartaglia et al, 1991) while the p55 TNF-R is generally known to mediate apoptosis (Tartaglia et al, 1993), a process in which the p75 TNF-R mav also be involved (Grell et al. 1995: Zheng et al, 1995).
Keywords
- Tumor Necrosis Factor Receptor
- Contact Hypersensitivity
- Lymphoid Structure
- Tertiary Lymphoid Structure
- Tumor Necrosis Factor Signalling
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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References
Akassoglou, K., Probert, L., Kontogeorgos, G. and Kollias, G., 1997, Astrocyte-specific but not neuron-specific transmembrane TNF triggers inflammation and degeneration in the central nervous system of transgenic mice. J.Immunol., 158: 438.
Bromberg, J.S., Chavin, K.D. and Kunkel, S.L., 1992, Anti-tumour necrosis factor antibodies suppress cell-mediated immunity in vivo. J.Immunol., 148: 3412.
Browning, J.L., Ngamek, 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 beta, a novel member of the TNF family that forms a heteromeric complex with lymphotoxin on the cell surface. Cell. 72: 847.
Crowe, P.D., VanArsdale, T.L., Walter, B.N., Ware, C.F., Hession, C., Ehrenfels, B., Browning, J.L., Din, W.S., Goodwin, R.G. and Smith, C.A., 1994, A lymphotoxin-beta-specific receptor. Science. 264: 707.
Cumberbatch, M., and Kimber, I., 1992. Dermal tumour necrosis factor-alpha induces dendritic cell migration to draining lymph nodes, and possibly provides one stimulus for Langerhan’s cell migration. Immunology. 75: 257.
Dalton, D.K., Pitts-Meek, S., Keshav, S., Figari, I.S., Bradley, A. and Stewart, T.A., 1993 Multiple defects of immune cell function in mice with disrupted interferon-gamma genes. Science. 259: 1739.
Douni, E., Akassoglou, K., Alexopoulou, L., Georgopoulos, S., Haralambous, S., Hill, S., Kassiotis, G., Kontoyiannis, D., Pasparakis, M., Plows, D., Probert, L. and Kollias, G. 1996, Transgenic and knockout analyses of the role of TNF in immune regulation and disease pathogenesis. J. Inflamm., 47: 27.
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 tumour-necrosis factor but normal T-cell development in TNF receptors-deficient mice. Nature. 372: 560.
Espevik, T., Brockhaus, M., Loetscher, H., Nonstad, U. and Shalaby, R., 1990, Characterization of binding and biological effects of monoclonal antibodies against a human tumour necrosis factor receptor. J.Exp.Med., 171: 415.
Georgopoulos, S., Plows, D. and Kollias, G., 1996, Transmembrane TNF is sufficient to induce localized tissue toxicity and chronic inflammatory arthritis in transgenic mice. J. Inflamm. 46: 86.
Grell, M., Douni, E., Wajant, H., Lohden, M., Clauss, M., Maxeiner, B., Georgopoulos, S., Lesslauer, W., Kollias, G., Pfizenmaier, K. and Scheurich, P., 1995, The trans-membrane form of tumor necrosis factor is the prime activating ligand of the 80 kDa tumor necrosis factor receptor. Cell. 83: 793.
Harty, J.T. and Bevan, M.J., 1995, Specific immunity to Listeria monocytogenes in the absence of IFN amma. Immunity. 3: 109.
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 and full antibody responses require tumor necrosis factor receptor-1 signaling. J.Exp.Med., 183: 2367.
Keffer, J., Probert, L., Cazlaris, H., Georgopoulos, S., Kaslaris, E., Kioussis, D. and Kollias, G., 1991, Transgenic mice expressing human tumour necrosis factor: a predictive genetic model of arthritis. EMBO J., 10: 4025.
Kondo, S., Wang, B., Fujisawa, H., Shivji, G.M., Echtenacher, B., Mak, T.W., and Sauder, D.N., 1995, Effect of gene-targeted mutation in TNF receptor (p55) on contact hypersensitivity and ultraviolet B-induced immunosuppression. J.Immunol., 155: 3801.
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.
Kriegler, M., Perez, C., DeFay, K., Albert, I. and Lu, S.D., 1988, A novel form of TNF/cachectin is a cell surface cytotoxic transmembrane protein: ramifications for the complex physiology of TNF. Cell. 53: 45.
Kurimoto, I. and Streilein, J.W., 1992, cis-urocanic supression of contact hypersensitivity induction is mediated via tumour necrosis factor-á. J.Immunol. 148: 3072.
Leprince, C., Cohen-Kaminsky, S., Berrih-Aknin, S., Vernet-Der Garabedian, B., Treton, D., Galanaud, P., and Richard, Y., 1990, Thymic B cells from myasthenia gravis patients are activated B cells. Phenotypic and functional analysis. J.Immunol., 145: 2115.
Matsumoto, M., Mariathasan, S., Nahm, M.H., Baranyay, F., Peschon, J.J. and Chaplin, D.D., 1996a, Role of lymphotoxin and the type I TNF receptor in the formation of germinal centers. Science. 271: 1289.
Matsumoto, M., Lo, S.F., Carruthers, C.J., Min, J., Mariathasan, S., Huang, G., Plas, D.R., Martin, S.M., Geha, R.S., Nahm, M.H. and Chaplin, D.D. (1996b). Affinity maturation without germinal centres in lymphotoxin-alpha-deficient mice. Nature. 382: 462.
Neumann, B., Machleidt, T., Lifka, A., Pfeffer, K., Vestweber, D., Mak, T.W., Holzmann, B. and Kronke, M., 1996, Crucial role of 55-kilodalton TNF receptor in TNF-induced adhesion molecule expression and leukocyte organ infiltration. J.Immunol., 156: 1587.
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.
Pasparakis, M., Alexopoulou, L., Douni, E. and Kollias, G., 1996b, Tumour necrosis factors in immune regulation: everything that’s interesting is new! Cytokine and Growth Factor Review, 7: 223.
Pasparakis, M., Alexopoulou, L., Grell, M., Pfizenmaier, K., Bluethmann, H. and Kollias, G., 1997, Intact Peyer’s patch organogenesis yet defective formation of B lymphocyte follicles in peripheral lymphoid organs of mice deficient for tumour necrosis factor and its 55 kDa receptor. (Submitted for publication).
Paul, N.L., and Ruddle, N.H., 1988, Lymphotoxin. Annu.Rev.ImmunoL 6: 407.
Pfeffer, K., Matsuyama, T., Kundig, T.M., Wakeham, A., Kishihara, K., Shahinian, A., Wiegmann, K., Ohashi, P.S., Kronke, 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.
Piguet, P.F., Grau, G.E., Hauser, C. and Vassalli, P., 1991, Tumour necrosis factor is a critical mediator in hapten induced irritant and contact hypersensitivity reactions. J.Exp.Med., 173: 673.
Probert, L., Plows, D., Kontogeorgos, G. and Kollias, G., 1995b, The type I interleukin-1 receptor acts inseries with tumor necrosis factor (TNF) to induce arthritis in TNF-transgenic mice. Eur.J.Immunol., 25: 1794.
Probert, L., Keffer, J., Corbella, P., Cazlaris, H., Patsavoudi, E., Stephens, S., Kaslaris, E., Kioussis, D. and Kollias, G., 1993, Wasting, ischemia, and lymphoid abnormalities in mice expressing T cell-targeted human tumor necrosis factor transgenes. J.Immunol., 151: 1894.
Probert, L., Akassoglou, K., Pasparakis, M., Kontogeorgos, G. and Kollias, G., 1995a, Spontaneous inflammatory demyelinating disease in transgenic mice showing central nervous system-specific expression of tumor necrosis factor alpha. Proc.Natl.Acad. Sci. USA. 92: 11294.
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.
Tartaglia, L.A., Weber, R.F., Figari, I.S., Reynolds, C., Palladino, M.A. and Goeddel D.V., 1991, The two different receptors for tumour necrosis factor mediate distinct cellular responses. Proc.Natl.Acad.Sci. USA. 88: 9292.
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.
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. and Chaplin, D., 1994, Abnormal development of peripheral lymphoid organs in mice deficient in lymphotoxin. Science. 264: 703.
Vandenabeele, P. Declercq, W., Beyaert, R. and Fiers, W., 1995, Two tumour necrosis factor receptors: structure and function. Trends Cell Biol. 5: 392.
Vassali, P., 1992, The pathophysiology of tumour necrosis factor. Annu.Rev.Immunol. 10: 411.
Wang, B., Kondo, S., Shivji, G.M., Fujisawa, H., Mak, T.W. and Sauder, D.N., 1996, Tumour necrosis factor receptor II (p75) signalling is required for the migration of Langerhans’ cells. Immunology. 88: 284.
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.
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Pasparakis, M., Douni, E., Alexopoulou, L., Kollias, G. (1997). The Role of Tumour Necrosis Factor in Lymphoid Tissue Formation and Function. In: Gregoriadis, G., McCormack, B., Allison, A.C. (eds) Vaccine Design. NATO ASI Series, vol 293. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-0062-3_2
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