Lymphotoxin/light, lymphoid microenvironments and autoimmune disease

Nature Reviews Immunology

Volumn 3, Issue 8, 2003, Pages 642-655

  Gommerman, Jennifer L ^a   Browning, Jeffrey L ^a  

^a BIOGEN   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

LYMPHOTOXIN; TUMOR NECROSIS FACTOR RECEPTOR;

AUTOIMMUNE DISEASE; AUTOIMMUNITY; IMMUNE RESPONSE; IMMUNE SYSTEM; LYMPHOID ORGAN; MICROENVIRONMENT; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; ANIMAL; DRUG ANTAGONISM; FOLLICULAR DENDRITIC CELL; HUMAN; IMMUNOLOGY; LYMPHOID TISSUE;

ANIMALS; AUTOIMMUNE DISEASES; DENDRITIC CELLS, FOLLICULAR; HUMANS; LYMPHOID TISSUE; LYMPHOTOXIN-ALPHA; RECEPTORS, TUMOR NECROSIS FACTOR; SIGNAL TRANSDUCTION;

EID: 0141832116     PISSN: 14741733     EISSN: None     Source Type: Journal    
DOI: 10.1038/nri1151     Document Type: Review

References (155)

1. Goodnow, C. C. Chance encounters and organized rendezvous. Immunol. Rev. 166, 5-10 (1997).
2. Aggarwal, B. B. & Natarajan, K. Tumor necrosis factors: developments during the last decade. Eur. Cytokine Netw. 7, 93-124 (1996).
3. Ware, C. F., VanArsdale, T. L., Crowe, P. D. & Browning, J. L. The ligands and receptors of the lymphotoxin system. Curr. Top. Microbiol. Immunol. 198, 175-218 (1995).
4. Mebius, R. E. Organogenesis of lymphoid tissues. Nature Rev. Immunol. 3, 292-303 (2003).
5. Muller, G. & Lipp, M. Concerted action of the chemokine and lymphotoxin system in secondary lymphoid-organ development. Curr. Opin. Immunol. 15, 217-224 (2003).
6. Luther, S. A. Lopez, T., Bai, W., Hanahan, D. & Cyster, J. G. BLC expression in pancreatic islets causes B cell recruitment and lymphotoxin-dependent lymphoid neogenesis. Immunity 12, 471-481 (2000). This paper nicely shows that ectopic expression of a chemokine was sufficient to induce organized lymphoid structures.
7. Ruddle, N. H. Lymphoid neo-organogenesis: lymphotoxin's role in inflammation and development. Immunol. Res. 19, 119-125 (1999).
8. Vinuesa, C. G. & Cook, M. C. The molecular basis of lymphoid architecture and B cell responses: implications for immunodeficiency and immunopathology. Curr. Mol. Med. 1, 689-725 (2001).
9. Granger, S. W. & Ware, C. F. Turning on LIGHT. J. Clin. Invest. 108, 1741-1742 (2001).
10. Murphy, M. et al. Expression of the lymphotoxin-β receptor on follicular stromal cells in human lymphoid tissues. Cell Death Differ. 5, 497-505 (1998).
11. Browning, J. L. et al. Characterization of lymphotoxin-αβ complexes on the surface of mouse lymphocytes. J. Immunol. 159, 3288-3298 (1997).
12. Browning, J. L. & French, L. E. Visualization of lymphotoxin-β and lymphotoxin-β receptor expression in mouse embryos. J. Immunol. 168, 5079-5087 (2002).
13. De Togni, P. et al. Abnormal development of peripheral lymphoid organs in mice deficient in lymphotoxin. Science 264, 703-707 (1994). The first study that linked lymphotoxin (LT) to lymph-node development.
14. Rennert, P. D. TNF family ligands and receptors control the development of secondary lymphoid organs. Recent Res. Devel. Immunity 1, 33-43 (2003).
15. Finke, D. & Kraehenbuhl, J. P. Formation of Peyer's patches. Curr. Opin. Genet. Dev. 11, 561-567 (2001).
16. Fu, Y. X. & Chaplin, D. D. Development and maturation of secondary lymphoid tissues. Annu. Rev. Immunol. 17, 399-433 (1999).
17. Scheu, S. et al. Targeted disruption of LIGHT causes defects in co-stimulatory T cell activation and reveals cooperation with lymphotoxin β in mesenteric lymph node genesis. J. Exp. Med. 195, 1613-1624 (2002).
18. Zhang, M., Guo, R., Zhai, Y., Fu, X. Y. & Yang, D. Light stimulates IFN-γ-mediated intercellular adhesion molecule-1 upregulation of cancer cells. Human Immunol. 64, 416-426 (2003).
19. Ye, Q. et al. Modulation of LIGHT-HVEM co-stimulation prolongs cardiac allograft survival. J. Exp. Med. 195, 795-800 (2002).
20. Shaikh, R. B. et al. Constitutive expression of LIGHT on T cells leads to lymphocyte activation, inflammation, and tissue destruction. J. Immunol. 167, 6330-6337 (2001).
21. Wang, J. et al. The regulation of T cell homeostasis and autoimmunity by T cell-derived LIGHT. J. Clin. Invest. 108, 1771-1780 (2001). This work, together with reference 20, using genetically altered mice, provided the first insights into the potential linkage between LIGHT and autoimmunity.
22. Cyster, J. G. et al. Follicular stromal cells and lymphocyte homing to follicles. Immunol. Rev. 176, 181-193 (2000).
23. Ansel, K. M. et al. A chemokine-driven positive feedback loop organizes lymphoid follicles. Nature 406, 309-314 (2000).
24. Fu, Y. X., Huang, G., Wang, Y. & Chaplin, D. D. B lymphocytes induce the formation of follicular dendritic cell clusters in a lymphotoxin-α -dependent fashion. J. Exp. Med. 187, 1009-1018 (1998).
25. Gonzalez, M., Mackay, F., Browning, J. L., Kosco-Vilbois, M. H. & Noelle, R. J. The sequential role of lymphotoxin and B cells in the development of splenic follicles. J. Exp. Med. 187, 997-1007 (1998).
26. Endres, R. et al. Mature follicular dendntic cell networks depend on expression of lymphotoxin-β receptor by radioresistant stromal cells and of lymphotoxin-β and tumor necrosis factor by B cells. J. Exp. Med. 189, 159-168 (1999).
27. Wu, Q. et al. The requirement of membrane lymphotoxin for the presence of dendritic cells in lymphoid tissues. J. Exp. Med. 190, 629-638 (1999).
28. Tumanov, A. et al. Distinct role of surface lymphotoxin expressed by B cells in the organization of secondary lymphoid tissues. Immunity 17, 239-250 (2002).
29. Mackay, F. & Browning, J. L. Turning off follicular dendritic cells. Nature 395, 26-27 (1998). This study showed that follicular dendritic-cell (FDC) networks were not static, but highly plastic even when fully developed.
30. Gommerman, J. L. et al. Manipulation of lymphoid microenvironments in nonhuman primates by an inhibitor of the lymphotoxin pathway. J. Clin. Invest. 110, 1359-1369 (2002).
31. Husson, H. et al. Functional effects of TNF and lymphotoxin α1β2 on FDC-like cells. Cell. Immunol. 203, 134-143 (2000).
32. Balogh, P., Aydar, Y., Tew, J. G. & Szakal, A. K. Appearance and phenotype of murine follicular dendritic cells expressing VCAM-1. Anat. Rec. 268, 160-168 (2002).
33. Matsushima, A. et al. Essential role of nuclear factor (NF)-κB-inducing kinase and inhibitor of κB (IκB) kinase α in NF-κB activation through lymphotoxin β receptor, but not through tumor necrosis factor receptor1. J. Exp. Med. 193, 631-636 (2001).
34. Yoshida, H. et al. Expression of α4β7 integrin defines a distinct pathway of lymphoid progenitors committed to T cells, fetal intestinal lymphotoxin producer, NK, and dendritic cells. J. Immunol. 167, 2511-2521 (2001).
35. Martin, F. & Kearney, J. F. Marginal-zone B cells. Nature Rev. Immunol. 2, 323-335 (2002).
36. Lu, T. T. & Cyster, J. G. Integrin-mediated long-term B cell retention in the splenic marginal zone. Science 297, 409-412 (2002).
37. Ettinger, R. et al. A critical role for lymphotoxin-β receptor in the development of diabetes in nonobese diabetic mice. J. Exp. Med. 193, 1333-1340 (2001). This study and a related study (reference 85) indicated a crucial role for the LT/LIGHT pathway in the development of diabetes in non-obese diabetic (NOD) mice.
38. Komer, H. et al. Recirculating and marginal zone B cell populations can be established and maintained independently of primary and secondary follicles. Immunol. Cell. Biol. 79, 54-61 (2001).
39. Mackay, F., Majeau, G. R., Lawton, P., Hochman, P. S. & Browning, J. L. Lymphotoxin but not tumor necrosis factor functions to maintain splenic architecture and humoral responsiveness in adult mice. Eur. J. Immunol. 27, 2033-2042 (1997).
40. Ngo, V. N., Comall, R. J. & Cyster, J. G. Splenic T zone development is B cell dependent. J. Exp. Med. 194, 1649-1660 (2001).
41. Cyster, J. G. Chemokines and cell migration in secondary lymphoid organs. Science 286, 2098-2102 (1999).
42. Ngo, V. N. et al. Lymphotoxin α/β and tumor necrosis factor are required for stromal cell expression of homing chemokines in B and T cell areas of the spleen. J. Exp. Med. 189, 403-412 (1999). In this work, lymphotoxin was directly linked to the release of several of the homeostatic chemokines.
43. Cyster, J. G. Leukocyte migration: scent of the T zone. Curr. Biol. 10, R30-R33 (2000).
44. Neutra, M. R., Mantis, N. J. & Kraehenbuhl, J. P. Collaboration of epithelial cells with organized mucosal lymphoid tissues. Nature Immunol. 2, 1004-1009 (2001).
45. H2 cell-type colitis. J. Immunol. 167, 2781-2790 (2001). The first paper to show that Peyer's-patch and colonic-patch cellularity was affected by LTβ receptor (LTβR) signalling in adult mice.
46. Debard, N., Sierro, F., Browning, J. & Kraehenbuhl, J. P. Effect of mature lymphocytes and lymphotoxin on the development of the follicle-associated epithelium and M cells in mouse Peyer's patches. Gastroenterol. 120, 1173-1182 (2001).
47. Spahn, T. W. et al. Induction of colitis in mice deficient of Peyer's patches and mesenteric lymph nodes is associated with increased disease severity and formation of colonic lymphoid patches. Am. J. Pathol. 161, 2273-2282 (2002).
48. Jacob, E., Baker, S. J. & Swaminathan, S. P. 'M' cells in the follicle-associated epithelium of the human colon. Histopathol. 11, 941-952 (1987).
49. Hamada, H. et al. Identification of multiple isolated lymphoid follicles on the antimesenteric wall of the mouse small intestine. J. Immunol 168, 57-64 (2002).
50. Lorenz, R. G., Chaplin, D. D., McDonald, K. G., McDonough, J. S. & Newberry, R. D. Isolated lymphoid follicle formation is inducible and dependent upon lymphotoxin-sufficient B lymphocytes, lymphotoxin-β receptor, and TNF receptor I function. J. Immunol. 170, 5475-5482 (2003).
51. Takemura, S. et al. Lymphoid neogenesis in rheumatoid synovitis. J. Immunol. 167, 1072-1080 (2001).
52. Banks, T. A. et al. Lymphotoxin-α-deficient mice. Effects on secondary lymphoid organ development and humoral immune responsiveness. J. Immunol. 155, 1685-1693 (1995).
53. Koni, P. A. et al. Distinct roles in lymphoid organogenesis for lymphotoxins α and β revealed in lymphotoxin β-deficient mice. Immunity 6, 491-500 (1997).
54. Kang, H. S. et al. Signaling via LTβR on the lamina propria stromal cells of the gut is required for IgA production. Nature Immunol. 3, 576-582 (2002). This study directly linked LTβR-mediated control of a mucosal microenvironment to the production of immunoglobulin A.
55. Newberry, R. D., McDonough, J. S., McDonald, K. G. & Lorenz, R. G. Postgestational lmphotoxin/lymphotoxin β receptor interactions are essential for the presence of intestinal B lymphocytes. J. Immunol. 168, 4988-4997 (2002).
56. Fagarasan, S. & Honjo, T. Intestinal IgA synthesis: regulation of front-line body defences. Nature Rev. Immunol. 3, 63-72 (2003).
57. Itoh, M. et al. Deletion of bone marrow stromal cell antigen-1 (CD157) gene impaired systemic thymus independent-2 antigen-induced IgG3 and mucosal TD antigen-elicited IgA responses. J. Immunol. 161, 3974-3983 (1998).
58. Wang, J. et al. The complementation of lymphotoxin deficiency with LIGHT, a newly discovered TNF family member, for the restoration of secondary lymphoid structure and function. Eur. J. Immunol. 32, 1969-1979 (2002).
59. Yamada, T. et al. Abnormal immune function of hemopoietic cells from alymphoplasia (aly) mice, a natural strain with mutant NF-κB-inducing kinase. J. Immunol. 165, 804-812 (2000).
60. Karrer, U., Althage, A., Odermatt, B., Hengartner, H. & Zinkemagel, R. M. Immunodeficiency of alymphoplasia mice (aly/aly) in vivo: structural defect of secondary lymphoid organs and functional B cell defect. Eur. J. Immunol. 30, 2799-2807 (2000).
61. Pomerantz, J. L. & Baltimore, D. Two pathways to NF-κB. Mol. Cell 10, 693-695 (2002).
62. Ghosh, S. & Karin, M. Missing pieces in the NF-κB puzzle. Cell 109, S81-S96 (2002).
63. Rennert, P. D. et al. Essential role of lymph nodes in contact hypersensitivity revealed in lymphotoxin-α-deficient mice. J. Exp. Med. 193, 1227-1238 (2001).
64. Koni, P. A. & Flavell, R. A. Lymph node germinal centers form in the absence of follicular dendritic cell networks. J. Exp. Med. 189, 855-864 (1999).
65. de Vinuesa, C. G. et al. Germinal centers without T cells. J. Exp. Med. 191, 485-494 (2000).
66. Futterer, A., Mink, K., Luz, A., Kosco-Vilbois, M. H. & Pfeffer, K. The lymphotoxin β receptor controls organogenesis and affinity maturation in peripheral lymphoid tissues. Immunity 9, 59-70 (1998).
67. Matsumoto, M. et al. Affinity maturation without germinal centres in lymphotoxin-α-deficient mice. Nature 382, 462-466 (1996). These authors showed that FDC networks and germinal centres do not form in the absence of expression of LT.
68. Hannum, L. G., Haberman, A. M., Anderson, S. M. & Shiomchik, M. J. Germinal center initiation, variable gene region hypermutation, and mutant B cell selection without detectable immune complexes on follicular dendritic cells. J. Exp. Med. 192, 931-942 (2000).
69. William, J., Euler, C., Christensen, S. & Shlomchik, M. J. Evolution of autoantibody responses via somatic hypermutation outside of germinal centers. Science 297, 2066-2070 (2002).
70. Maccioni, M. et al. Arthritogenic monoclonal antibodies from K/BxN mice. J. Exp. Med. 195, 1071-1077 (2002).
71. Holmdahl, R. et al. Type II collagen autoimmunity in animals and provocations leading to arthritis. Immunol. Rev. 118, 193-232 (1990).
72. Fava, R. F. et al. A role for the lymphotoxin/LIGHT axis in the pathogenesis of murine collagen induced arthritis. J. Immunol. 171, 115-126 (2003).
73. + T cell responses: the alternative approaches Annu. Rev. Immunol. 15, 297-322 (1997).
74. H2 differentiation. J. Immunol. 162, 1333-1338 (1999).
75. Mackay, F. et al. Both the lymphotoxin and tumor necrosis factor pathways are involved in experimental murine models of colitis. Gastroenterol. 115, 1464-1475 (1998). This work on colitis provided one of the first hints of a role for the LT/LIGHT system in T-cell function, as opposed to the many lines of evidence that link LT to B-cell function.
76. Suresh, M. et al. Role of Lymphotoxin α in T-cell responses during an acute viral infection. J. Virol. 76, 3943-3951 (2002).
77. Lund, F. E. et al. Lymphotoxin-α-deficient mice make delayed, but effective, T and B cell responses to influenza. J. Immunol. 169, 5236-5243 (2002).
78. Benedict, C. A. et al. Lymphotoxins and cytomegalovirus cooperatively induce interferon-β, establishing host-virus detente. Immunity 15, 617-626 (2001).
79. Lee, B. J., Santee, S., Von Gesjen, S., Ware, C. F. & Sarawar, S. R. Lymphotoxin-α-deficient mice can clear a productive infection with murine γ-herpesvirus 68 but fail to develop splenomegaly or lymphocytosis. J. Virol. 74, 2786-2792 (2000).
80. + T cell responses and fail to contain virus infection of the central nervous system. J. Immunol. 166, 1066-1074 (2001).
81. Muller, S. et al. Role of an intact splenic microarchitecture in early lymphocytic chonomeningitis virus production. J. Virol. 76, 2375-2383 (2002).
82. Berger, D. P. et al. Lymphotoxin-α-deficient mice show defective antiviral immunity. Virology 260, 136-147 (1999).
83. + T-cell response to lymphocytic choriomeningitis virus (LCMV).
84. + T-cell-mediated graft rejection that was independent from LIGHT, thereby showing that not all T-cell mediated events inhibited by a LTβR-immunoglobulin fusion protein were due to the loss of LIGHT signalling.
85. Wu, Q. et al. Reversal of spontaneous autoimmune insulitis in nonobese diabetic mice by soluble lymphotoxin receptor. J. Exp. Med. 193, 1327-1332 (2001).
86. Rimington, S. D. et al. 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 (1998).
87. Suen, W. E., Bergman, C. M., Hjelmstrom, P. & Ruddle, N. H. A critical role for lymphotoxin in experimental allergic encephalomyelitis. J. Exp. Med. 186, 1233-1240 (1997).
88. Gommerman, J. L. et al. A role for surface lymphotoxin in experimental autoimmune encephalitis indepdendent of LIGHT. J. Clin. Invest. On the press).
89. Tamada, K. et al. Modulation of T-cell-mediated immunity in tumor and graft-versus-host disease models through the LIGHT co-stimulatory pathway. Nature Med. 6, 283-289 (2000).
90. Tamada, K. et al. Blockade of LIGHT/LTβ and CD40 signaling induces allospecific T cell anergy, preventing graft-versus-host disease. J. Clin. Invest. 109, 549-557 (2002).
91. + T cell function in mice lacking the TNF superfamily member LIGHT. J. Immunol. 168, 4832-4835 (2002).
92. Kassiotis, G. & Kollias, G. Uncoupling the proinflammatory from the immunosuppressive properties of tumor necrosis factor (TNF) at the p55 TNF receptor level: implications for pathogenesis and therapy of autoimmune demyelination. J. Exp. Med. 193, 427-434 (2001).
93. TNF neutralization in MS: results of a randomized, placebo-controlled multicenter study. The Lenercept multiple sclerosis study group and the University of British Columbia MS/MRI analysis group. Neurology 53, 457-465 (1999).
94. Weyand, C. M., Kurtin, P. J. & Goronzy, J. J. Ectopic lymphoid organogenesis: a fast track for autoimmunity. Am. J. Pathol. 159, 787-793 (2001).
95. Mazzucchelli, L. et al. BCA-1 is highly expressed in Helicobacter pylori-induced mucosa-associated lymphoid tissue and gastric lymphoma. J. Clin. Invest. 104, R49-R54 (1999).
96. Mabbott, N. A. & Bruce, M. E. Follicular dendritic cells as targets for intervention in transmissible spongiform encephalopathies. Semin. Immunol. 14, 285-293 (2002).
97. Mabbott, N. A., Young, J., McConnell, I. & Bruce, M. E. Follicular dendritic cell dedifferentiation by treatment with an inhibitor of the lymphtoxin pathway dramatically reduces scrapie susceptability. J. Virol. 77, 6845-6854 (2003).
98. Burton, G. F., Keele, B. F., Estes, J. D., Thacker, T. C. & Gartner, S. Follicular dendritic cell contributions to HIV pathogenesis Semin. Immunol. 14, 275-284 (2002).
99. Montgomery, R. I., Wamer, M. S., Lum, B. J. & Spear, P. G. Herpes simplex virus-1 entry into cells mediated by a novel member of the TNF/NGF receptor family. Cell 87, 427-436 (1996).
100. Pitti, R. M. et al. Genomic amplification of a decoy receptor for Fas ligand in lung and colon cancer. Nature 396, 699-703 (1998).
101. Yu, K. Y. et al. A newly identified member of tumor necrosis factor receptor superfamily (TR6) suppresses LIGHT-mediated apoptosis. J. Biol. Chem 274, 13733-13736 (1999).
102. Migone, T. S. et al. TL1A is a TNF-like ligand for DR3 and TR6/DcR3 and functions as a T cell co-stimulator. Immunity 16, 479-492 (2002).
103. Baud, V. & Karin, M. Signal transduction by tumor necrosis and its relatives. Trends Cell Biol. 11, 372-377 (2001).
104. Chen, M. C. et al. The role of apoptosis signal-regulating kinase 1 in lymphotoxin-β receptor-mediated cell death J. Biol. Chem. 278, 16073-16081 (2003).
105. MacEwan, D. J. TNF ligands and receptors - a matter of life and death. Br. J. Pharmacol. 135, 855-875 (2002).
106. H2 paradigm. J. Exp. Med. 192, F31-F34 (2000).
107. Luther, S. A. et al. Differing activities of homeostatic chemokines CCL19, CCL21, and CXCL12 in lymphocyte and dendritic cell recruitment and lymphoid neogenesis. J. Immunol. 169, 424-433 (2002).
108. Vissers, J. L. M., Hartgers, F. C., Lindhout, E., Figdor, C. G. & Adema, G. J. BLC (CXCL13) is expressed by different denddtic cell subsets in vitro and in vivo. Eur. J. Immunol. 31, 1544-1549 (2001).
109. + dendritic cells in murine lupus and preferential chemotaxis of B1 cells towards BLC. J. Exp. Med. 193, 1393-1402 (2001).
110. Ansel, K. M., Harris, R. B. & Cyster, J. G. CXCL13 is required for B1 cell homing, natural antibody production, and body cavity immunity. Immunity 16, 67-76 (2002).
111. Gretz, J. E., Anderson, A. O. & Shaw, S. Cords, channels, corridors and conduits: critical architectural elements facilitating cell interactions in the lymph node cortex. Immunol. Rev. 166, 11-24 (1997).
112. Okada, S., Albrecht, R. M., Ahannejad, S. & Schraufnagel, D. E. Structural aspects of the lymphocyte traffic in rat submandibular lymph node. Microsc. Mibroanal. 8, 116-133 (2002).
113. Drayton, D. I., Ying, X., Lee, J., Lesslauer, W. & Ruddle, N. H. Ectopic LTαβ directs lymphoid organ neogenesis with concomitant expression of peripheral lymph node addressin and a HEV-restricted sulfotransferase. J. Exp. Med. 197, 1153-1163 (2003).
114. Mebius, R. E., Streeter, P. R., Breve, J., Duijvestijn, A. M. & Kraal, G. The influence of afferent lymphatic vessel interruption on vascular addressin expression. J. Cell. Biol. 115, 85-95 (1991).
115. Gretz, J. E., Norbury, C. C., Anderson, A. O., Proudfoot, A. E. & Shaw, S. Lymph-borne chemokines and other low molecular weight molecules reach high endothelial venules via specialized conduits while a functional barrier limits access to the lymphocyte microenvironments in lymph node cortex. J. Exp. Med. 192, 1425-1440 (2000). A good introduction to the problems of lymph flow and compartments in the lymph node.
116. Fan, L., Reilly, C. R., Luo, Y., Dorf, M. E. & Lo, D. Ectopic expression of the chemokine TCA4/SLC is sufficient to trigger lymphoid neogenesis. J. Immunol. 164, 3955-3959 (2000).
117. Chen, S. C. et al. Ectopic expression of the murine chemokines CCL21 a and CCL21b induces the formation of lymph node-like structures in pancreas, but not skin, of transgenic mice. J. Immunol. 168, 1001-1008 (2002).
118. van Nierop, K. & de Groot, C. Human follicular dendritic cells: function, origin and development. Semin. Immunol. 14, 251-257 (2002).
119. Kim, H. J., Krenn, V., Steinhauser, G. & Berek, C. Plasma cell development in synovial germinal centers in patients with rheumatoid and reactive arthritis. J. Immunol. 162, 3053-3062 (1999).
120. Noguchi, M., Hiwatashi, N., Liu, Z. & Toyota, T. Secretion imbalance between tumour necrosis factor and its inhibitor in inflammatory bowel disease. Gut 43, 203-209 (1998).
121. Sankary, H. et al. Daily determinations of serum lymphotoxin allows for accurate early diagnosis of hepatic allograft rejection. Transplant. Proc. 25, 926-930 (1993).
122. Ishibashi, K., Kodama, M., Hanada, S. & Arima, T. Tumor necrosis factor-β and hypercalcemia. Leuk. Lymphoma 7, 409-417 (1992).
123. Mackay, F. et al. Cytotoxic activities of recombinant soluble murine lymphotoxin-α and lymphotoxin-αβ complexes. J. Immunol. 159, 3299-3310 (1997).
124. Cuff, C. A., Sacca, R. & Ruddle, N. H. Differential induction of adhesion molecule and chemokine expression by LTα3 and LTαβ in inflammation elucidates potential mechanisms of mesenteric and and peripheral lymph node development. J. Immunol. 162, 5965-5972 (1999).
125. Roach, D. R. et al. Secreted lymphotoxin-α is essential for the control of an intracellular bacterial infection. J. Exp. Med. 193, 239-246 (2001).
126. Kuprash, D. V. et al. Redundancy in tumor necrosis factor (TNF) and lymphotoxin (LT) signaling in vivo: mice with inactivation of the entire TNF/LT locus versus single-knockout mice. Mol. Cell. Biol. 22, 8626-8634 (2002).
127. Chicheportiche, Y. et al. TWEAK, a new secreted ligand in the tumor necrosis factor family that weakly induces apoptosis. J. Biol. Chem. 272, 32401-32410 (1997).
128. Mauri, D. N. et al. LIGHT, a new member of the TNF superfamily, and lymphotoxin α are ligands for herpesvirus entry mediator. Immunity 8, 21-30 (1998).
129. Harmsen, A. et al. Cutting edge: organogenesis of nasal-associated lymphoid tissue (NALT) occurs independently of lymphotoxin-α (LTα) and retinoic acid receptor-related orphan receptor-gamma, but the organization of NALT is LTα dependent. J. Immunol. 168, 986-990 (2002).
130. + cells. Immunity 17, 31-40 (2002).
131. Lian, R. H. & Kumar, V. Murine natural killer cell progenitors and their requirements for devalopment. Semin. Immunol. 14, 453-460 (2002).
132. Yu, P. et al. B cells control the migration of a subset of dendritic cells into B cell follicles via CXC ligand 13 in a lymphotoxin-dependent fashion. J. Immunol. 168, 5117-5123 (2002).
133. Kratz, A., Campos-Neto, A., Hanson, M. S. & Ruddle, N. H. Chronic inflammation caused by lymphotoxin is lymphoid neogenesis. J. Exp. Med. 183, 1461-1472 (1996). The key paper that first described the ability of ectopic expression of LT to drive the formation of organized lymphoid structures.
134. Wang, J. & Fu, Y. X. LIGHT (a cellular ligand for herpes virus entry mediator and lymphotoxin receptor)-mediated thymocyte deletion is dependent on the interaction between TCR and MHC/self-peptide. J. Immunol. 170, 3986-3993 (2003).
135. Steiniger, B., Barth, P. & Hallinger, A. The perifollicular and marginal zones of the human splenic white pulp: do fibroblasts guide lymphocyte immigration? Am. J. Pathol. 159, 501-512 (2001).
136. Castenholz, A. Architecture of the lymph node with regard to its function. Curr. Top. Pathol. 84, 1-32 (1990).
137. Millet, I. & Ruddle, N. H. Differential regulation of lymphotoxin (LT), lymphotoxin-β (LT-β), and TNF-α in murine T cell clones activated through the TCR. J. Immunol. 152, 4336-4346 (1994).
138. + T cells are a major source of lymphotoxin α. J. Immunol. 162, 3790-3794 (1999).
139. Voon, D. C., Subrata, L. S. & Abraham, L. J. Regulation of lymphotoxin-β by tumor necrosis factor, phorbol myristate acetate, and ionomycin in Jurkat T cells. J. Interferon Cytokine Res. 21, 921-930 (2001).
140. Kuprash, D. V. et al. Cyclosporin A blocks the expression of lymphotoxin α, but not lymphotoxin β, in human peripheral blood mononuclear cells. Blood 100, 1721-1727 (2002).
141. Kashia, Y., Giorda, R., Herberman, R. B., Whiteside, T. L. & Vujanovic, N. L. Constitutive expression and role of the TNF family ligands in apoptotic killing of tumor cells by human NK cells. J. Immunol. 163, 5358-5366 (1999).
142. Yoshida, H. et al. Different cytokines induce surface lymphotoxin-αβ on IL-7 receptor-α cells that differentially engender lymph nodes and Peyer's patches. Immunity 17, 823-833 (2002).
143. Agyekum, S. et al. Expression of lymphotoxin-β (LT-β) in chronic inflammatory conditions. J. Pathol. 199, 115-121 (2003).
144. Tamada, K. et al. LIGHT, a TNF-like molecule, co-stimulates T cell proliferation and is required for dendritic cell-mediated allogeneic T cell response. J. Immunol. 164, 4105-4110 (2000). An important study that links LIGHT to acute graft-versus-host disease.
145. Pakala, S. V., Ilic, A., Chen, L. & Sarvetnick, N. TNF-α receptor 1 (p55) on islets is necessary for the expression of LIGHT on diabetogenic T cells. Clin. Immunol. 100, 198-207 (2001).
146. Zhai, Y. et al. LIGHT, a novel ligand for lymphotoxin β receptor and TR2/HVEM induces apoptosis and suppresses in vivo tumor formation via gene transfer. J. Clin. Invest. 102, 1142-1151 (1998).
147. Hochman, P. S., Majeau, G. R., Mackay, F. & Browning, J. L. Proinflammatory responses are efficiently induced by homotrimeric but not heterotrimeric lymphotoxin ligands. J. Inflamm. 46, 220-234 (1995).
148. Browning, J. L. et al. Signaling through the lymphotoxin β receptor induces the death of some adenocarcinoma tumor lines. J. Exp. Med. 183, 867-878 (1996).
149. Muller, P., Mannel, D. N. & Hehlgans, T. Functional characterization of the mouse lymphotoxin-β receptor promoter. Eur. Cytokine. Netw. 12, 325-330 (2001).
150. Morel, Y., Truneh, A., Sweet, R. W., Olive, D. & Costello, R. T. The TNF superfamily members LIGHT and CD154 (CD40 ligand) co-stimulate induction of dendritic cell maturation and elicit specific CTL activity J. Immunol. 167, 2479-2486 (2001).
151. Lee, W. H. et al. Tumor necrosis factor receptor superfamily 14 is involved in atherogenesis by inducing proinflammatory cytokines and matrix metalloproteinases. Arterioscler. Thromb. Vasc. Biol. 21, 2004-2010 (2001).
152. Matsui, H., Hikichi, Y., Tsuji, I., Yamada, T. & Shintani, Y. LIGHT, a member of the tumor necrosis factor ligand superfamily, prevents tumor necrosis factor-mediated human primary hepatocyte apoptosis, but not Fas mediated apoptosis. J. Biol. Chem. 277, 50054-50061 (2002).
153. Bai, C. et al. Overexpression of M68/DcR3 in human gastrointestinal tract tumors independent of gene amplification and its location in a four-gene cluster. Proc. Natl Acad. Sci. USA 97, 1230-1235 (2000).
154. Goluszko, E. et al. Lymphotoxin-α deficiency completely protects C57BL/6 mice from developing clinical experimental autoimmune myasthenia gravis. J. Neuroimmunol. 113, 109-118 (2001).
155. Frei, K. et al. Tumor necrosis factor α and lymphotoxin α are not requied for induction of acute experimental autoimmune encephalomyelitis. J. Exp. Med. 185, 2177-2182 (1997).