Gene Symbol: Lta
Description: lymphotoxin A
Alias: LT-[a], LT-alpha, LT[a], LTalpha, Ltx, TNF-beta, TNFSF1, Tnfb, Tnfsf1b, Tnlg1e, hlb382, lymphotoxin-alpha, TNF beta, tumor necrosis factor ligand 1e, tumor necrosis factor ligand superfamily member 1
Species: mouse
Products:     Lta

Top Publications

  1. Eberl G, Marmon S, Sunshine M, Rennert P, Choi Y, Littman D. An essential function for the nuclear receptor RORgamma(t) in the generation of fetal lymphoid tissue inducer cells. Nat Immunol. 2004;5:64-73 pubmed
    ..This early LTi cell-mediated activation of lymph node and Peyer's patch mesenchyma forms the necessary platform for the subsequent development of mature lymphoid tissues. ..
  2. Smyth M, Johnstone R, Cretney E, Haynes N, Sedgwick J, Korner H, et al. Multiple deficiencies underlie NK cell inactivity in lymphotoxin-alpha gene-targeted mice. J Immunol. 1999;163:1350-3 pubmed
    ..5- to 3-fold in LT-alpha-deficient mice, as compared with wild-type mice. Combined defects in NK cell development and effector function contribute to compromised NK cell antitumor function in LT-alpha-deficient mice. ..
  3. Rangel Moreno J, Moyron Quiroz J, Kusser K, Hartson L, Nakano H, Randall T. Role of CXC chemokine ligand 13, CC chemokine ligand (CCL) 19, and CCL21 in the organization and function of nasal-associated lymphoid tissue. J Immunol. 2005;175:4904-13 pubmed
    ..Unlike other lymphoid organs, NALT develops independently of lymphotoxin-alpha (LTalpha)...
  4. Eberl G, Littman D. Thymic origin of intestinal alphabeta T cells revealed by fate mapping of RORgammat+ cells. Science. 2004;305:248-51 pubmed
    ..Our results suggest that intestinal RORgammat+ cells are local organizers of mucosal lymphoid tissue. ..
  5. Guy Grand D, DiSanto J, Henchoz P, Malassis Seris M, Vassalli P. Small bowel enteropathy: role of intraepithelial lymphocytes and of cytokines (IL-12, IFN-gamma, TNF) in the induction of epithelial cell death and renewal. Eur J Immunol. 1998;28:730-44 pubmed
    ..This insures the rapid epithelial renewal of the villi, which in turn helps maintain the functional integrity of the barrier. ..
  6. Wu Q, Sun Y, Wang J, Lin X, Wang Y, Pegg L, et al. Signal via lymphotoxin-beta R on bone marrow stromal cells is required for an early checkpoint of NK cell development. J Immunol. 2001;166:1684-9 pubmed
    ..Lymphotoxin-alpha (LTalpha)(-/-) and LTbetaR(-/-) mice show a severe systemic reduction of NK cells, which provides an excellent model to ..
  7. Moyron Quiroz J, Rangel Moreno J, Kusser K, Hartson L, Sprague F, Goodrich S, et al. Role of inducible bronchus associated lymphoid tissue (iBALT) in respiratory immunity. Nat Med. 2004;10:927-34 pubmed
    ..Thus, iBALT functions as an inducible secondary lymphoid tissue for respiratory immune responses. ..
  8. Matsumoto M, Fu Y, Molina H, Chaplin D. Lymphotoxin-alpha-deficient and TNF receptor-I-deficient mice define developmental and functional characteristics of germinal centers. Immunol Rev. 1997;156:137-44 pubmed
    Mice deficient in LT alpha (LT alpha-/-) lack lymph nodes and Peyer's patches...
  9. Matsumoto M, Lo S, Carruthers C, Min J, Mariathasan S, Huang G, et al. Affinity maturation without germinal centres in lymphotoxin-alpha-deficient mice. Nature. 1996;382:462-6 pubmed
    ..Mice deficient in lymphotoxin-alpha (LT alpha-/- mice) have no lymph nodes or Peyer's patches, and fail to form germinal centres in the spleen...

More Information


  1. Wilhelm P, Riminton D, Ritter U, Lemckert F, Scheidig C, Hoek R, et al. Membrane lymphotoxin contributes to anti-leishmanial immunity by controlling structural integrity of lymphoid organs. Eur J Immunol. 2002;32:1993-2003 pubmed
    ..LTbeta-/-) and compared it to a unique series of LTalpha-, TNF- and TNF/LTalpha-gene-targeted mice on an identical genetic background (B6.LTalpha-/-, B6...
  2. Kabashima K, Banks T, Ansel K, Lu T, Ware C, Cyster J. Intrinsic lymphotoxin-beta receptor requirement for homeostasis of lymphoid tissue dendritic cells. Immunity. 2005;22:439-50 pubmed
    ..B cells are a key source of LT alpha 1 beta 2 for splenic DC homeostasis, and transgenic overexpression of LT alpha 1 beta 2 on B cells leads to ..
  3. Jang M, Kweon M, Iwatani K, Yamamoto M, Terahara K, Sasakawa C, et al. Intestinal villous M cells: an antigen entry site in the mucosal epithelium. Proc Natl Acad Sci U S A. 2004;101:6110-5 pubmed
    ..lymphoid tissue (GALT)]-null mice, such as in utero lymphotoxin beta receptor (LTbetaR)-Ig-treated, lymphotoxin alpha (LTalpha)(-/-), tumor necrosis factor/LTalpha(-/-), and inhibition of differentiation 2 (Id2)(-/-) mice...
  4. Yokota Y, Mansouri A, Mori S, Sugawara S, Adachi S, Nishikawa S, et al. Development of peripheral lymphoid organs and natural killer cells depends on the helix-loop-helix inhibitor Id2. Nature. 1999;397:702-6 pubmed
    ..Our results indicate that Id2 has an essential role in the generation of peripheral lymphoid organs and NK cells. ..
  5. Ito D, Back T, Shakhov A, Wiltrout R, Nedospasov S. Mice with a targeted mutation in lymphotoxin-alpha exhibit enhanced tumor growth and metastasis: impaired NK cell development and recruitment. J Immunol. 1999;163:2809-15 pubmed
    ..Although LTalpha is known to be expressed by NK cells as well as T and B lymphocytes, the requirement of LTalpha for NK cell ..
  6. Vondenhoff M, Desanti G, Cupedo T, Bertrand J, Cumano A, Kraal G, et al. Separation of splenic red and white pulp occurs before birth in a LTalphabeta-independent manner. J Leukoc Biol. 2008;84:152-61 pubmed publisher
    ..The postnatal development of the splenic white pulp, involving the influx of T cells, depends on LTalpha1beta2 expressed by B cells. ..
  7. Harmsen A, Kusser K, Hartson L, Tighe M, Sunshine M, Sedgwick J, et al. Cutting edge: organogenesis of nasal-associated lymphoid tissue (NALT) occurs independently of lymphotoxin-alpha (LT alpha) and retinoic acid receptor-related orphan receptor-gamma, but the organization of NALT is LT alpha dependent. J Immunol. 2002;168:986-90 pubmed
    ..we found that NALT was formed in the absence of CD4+CD3- cells, which are thought to be the embryonic source of LTalpha. However, we also found that NALT of LTalpha-/- animals was disorganized and lymphopenic, suggesting that the ..
  8. Kang H, Chin R, Wang Y, Yu P, Wang J, Newell K, et al. Signaling via LTbetaR on the lamina propria stromal cells of the gut is required for IgA production. Nat Immunol. 2002;3:576-82 pubmed
    ..Consistently, lymphoid tissue chemokines and adhesion molecules were reduced within the LP of LTalpha(-/-) and LTbetaR(-/-) mice...
  9. Tkachuk M, Bolliger S, Ryffel B, Pluschke G, Banks T, Herren S, et al. Crucial role of tumor necrosis factor receptor 1 expression on nonhematopoietic cells for B cell localization within the splenic white pulp. J Exp Med. 1998;187:469-77 pubmed
    ..In contrast to lymphotoxin alpha-deficient mice (LTalpha-/-), bone marrow or fetal liver transplantation did not correct the abnormal ..
  10. Kuprash D, Alimzhanov M, Tumanov A, Anderson A, Pfeffer K, Nedospasov S. TNF and lymphotoxin beta cooperate in the maintenance of secondary lymphoid tissue microarchitecture but not in the development of lymph nodes. J Immunol. 1999;163:6575-80 pubmed
    ..Most lymphotoxin alpha (ltalpha)- and all lymphotoxin beta receptor (ltbetar)-deficient mice are completely devoid of lymph nodes (..
  11. Ehlers S, Holscher C, Scheu S, Tertilt C, Hehlgans T, Suwinski J, et al. The lymphotoxin beta receptor is critically involved in controlling infections with the intracellular pathogens Mycobacterium tuberculosis and Listeria monocytogenes. J Immunol. 2003;170:5210-8 pubmed
    ..When mice deficient in LT alpha or LT beta were challenged intranasally with Mycobacterium tuberculosis, they showed a significant increase in ..
  12. Cook M, Korner H, Riminton D, Lemckert F, Hasbold J, Amesbury M, et al. Generation of splenic follicular structure and B cell movement in tumor necrosis factor-deficient mice. J Exp Med. 1998;188:1503-10 pubmed
    Secondary lymphoid tissue organogenesis requires tumor necrosis factor (TNF) and lymphotoxin alpha (LTalpha)...
  13. Roach D, Briscoe H, Saunders B, Britton W. Independent protective effects for tumor necrosis factor and lymphotoxin alpha in the host response to Listeria monocytogenes infection. Infect Immun. 2005;73:4787-92 pubmed resistance to Listeria monocytogenes infection is well established, the roles of the related cytokines lymphotoxin alpha (LTalpha) and lymphotoxin beta (LTbeta) are unknown...
  14. Vandenabeele P, Declercq W, Beyaert R, Fiers W. Two tumour necrosis factor receptors: structure and function. Trends Cell Biol. 1995;5:392-9 pubmed
    ..Recent research suggests that several TNF-R-associated proteins, including kinases, may initiate cytoplasmic signal transduction. ..
  15. Frei K, Eugster H, Bopst M, Constantinescu C, Lavi E, Fontana A. Tumor necrosis factor alpha and lymphotoxin alpha are not required for induction of acute experimental autoimmune encephalomyelitis. J Exp Med. 1997;185:2177-82 pubmed
    ..Tumor necrosis factor alpha (TNF-alpha) and lymphotoxin alpha (LT-alpha) are thought to be involved in the events leading to inflammatory demyelination in the central ..
  16. Abe K, Yarovinsky F, Murakami T, Shakhov A, Tumanov A, Ito D, et al. Distinct contributions of TNF and LT cytokines to the development of dendritic cells in vitro and their recruitment in vivo. Blood. 2003;101:1477-83 pubmed
    TNF/LTalpha/LTbeta (tumor necrosis factor/lymphotoxin-alpha/lymphotoxin-beta) triple knockout (KO) mice show a significant reduction of dendritic cell (DC) number in the spleen, presumably due to defective recruitment and/or production...
  17. Wu Q, Wang Y, Wang J, Hedgeman E, Browning J, Fu Y. The requirement of membrane lymphotoxin for the presence of dendritic cells in lymphoid tissues. J Exp Med. 1999;190:629-38 pubmed
    ..However, LTbetaR(-/-) mice show reduced numbers of DCs, similar to the mice lacking membrane LT alpha/beta...
  18. White A, Carragher D, Parnell S, Msaki A, Perkins N, Lane P, et al. Lymphotoxin a-dependent and -independent signals regulate stromal organizer cell homeostasis during lymph node organogenesis. Blood. 2007;110:1950-9 pubmed
    ..In addition, analysis of the lymph node anlagen in normal and lymphotoxin a (LTa)-deficient embryos shows that LTa-mediated signaling is required to sustain proliferation and survival of stromal ..
  19. Ngo V, Cornall R, Cyster J. Splenic T zone development is B cell dependent. J Exp Med. 2001;194:1649-60 pubmed
    ..Introduction of a B cell specific LTalpha transgene on to the LTalpha-deficient background restored splenic CCL21 and gp38 expression, DC numbers, and T ..
  20. Neumann B, Luz A, Pfeffer K, Holzmann B. Defective Peyer's patch organogenesis in mice lacking the 55-kD receptor for tumor necrosis factor. J Exp Med. 1996;184:259-64 pubmed
    b>Lymphotoxin alpha (LT-alpha) may form secreted homotrimers binding to p55 and p75 tumor necrosis factor (TNF) receptors or cell surface-bound heterotrimers with LT-beta that interact with the LT-beta receptor...
  21. Fukuyama S, Hiroi T, Yokota Y, Rennert P, Yanagita M, Kinoshita N, et al. Initiation of NALT organogenesis is independent of the IL-7R, LTbetaR, and NIK signaling pathways but requires the Id2 gene and CD3(-)CD4(+)CD45(+) cells. Immunity. 2002;17:31-40 pubmed
  22. Browning J, Sizing I, Lawton P, Bourdon P, Rennert P, Majeau G, et al. Characterization of lymphotoxin-alpha beta complexes on the surface of mouse lymphocytes. J Immunol. 1997;159:3288-98 pubmed
    The lymphotoxin-alpha beta complex (LT alpha beta) is found on the surface of activated lymphocytes and binds to a specific receptor called the LT beta receptor (LT beta R)...
  23. Wang Y, Huang G, Wang J, Molina H, Chaplin D, Fu Y. Antigen persistence is required for somatic mutation and affinity maturation of immunoglobulin. Eur J Immunol. 2000;30:2226-34 pubmed
    ..Thus, these data support a model in which prolonged availability of antigen is required for somatic mutation and affinity maturation, and FDC or adjuvants facilitate such processes by slowly releasing antigens. ..
  24. Matsumoto M, Iwamasa K, Rennert P, Yamada T, Suzuki R, Matsushima A, et al. Involvement of distinct cellular compartments in the abnormal lymphoid organogenesis in lymphotoxin-alpha-deficient mice and alymphoplasia (aly) mice defined by the chimeric analysis. J Immunol. 1999;163:1584-91 pubmed
    Both lymphotoxin-alpha (LTalpha)-deficient mice and alymphoplasia (aly) mice, a natural mutant strain, manifest a quite similar phenotype: lack of lymph nodes (LN) and Peyer's patches (PP), with disturbed spleen architecture...
  25. Pokholok D, Maroulakou I, Kuprash D, Alimzhanov M, Kozlov S, Novobrantseva T, et al. Cloning and expression analysis of the murine lymphotoxin beta gene. Proc Natl Acad Sci U S A. 1995;92:674-8 pubmed
    ..The LT-beta promoter region contains putative Ets-binding sites, suggesting that the expression of LT-beta may be regulated in part by Ets transcription factors whose pattern of lymphoid expression overlaps that of LT-beta. ..
  26. Mackay F, Bourdon P, Griffiths D, Lawton P, Zafari M, Sizing I, et al. Cytotoxic activities of recombinant soluble murine lymphotoxin-alpha and lymphotoxin-alpha beta complexes. J Immunol. 1997;159:3299-310 pubmed
    Human lymphotoxin-alpha (LT alpha) is found in a secreted form and on the surface of lymphocytes as a complex with a second related protein called lymphotoxin-beta (LT beta)...
  27. Mariathasan S, Matsumoto M, Baranyay F, Nahm M, Kanagawa O, Chaplin D. Absence of lymph nodes in lymphotoxin-alpha(LT alpha)-deficient mice is due to abnormal organ development, not defective lymphocyte migration. J Inflamm. 1995;45:72-8 pubmed
    Mice homozygous for a targeted null mutation of lymphotoxin-alpha (LT alpha) are born without lymph nodes (LN) or Peyer's patches (PP) and with altered splenic architecture...
  28. Sacca R, Turley S, Soong L, Mellman I, Ruddle N. Transgenic expression of lymphotoxin restores lymph nodes to lymphotoxin-alpha-deficient mice. J Immunol. 1997;159:4252-60 pubmed
    Lymphotoxin-alpha (LT alpha) has recently been demonstrated to be important in the development of lymph nodes (LN), Peyer's patches, and splenic organization, including the development of germinal centers...
  29. Nedospasov S, Hirt B, Shakhov A, Dobrynin V, Kawashima E, Accolla R, et al. The genes for tumor necrosis factor (TNF-alpha) and lymphotoxin (TNF-beta) are tandemly arranged on chromosome 17 of the mouse. Nucleic Acids Res. 1986;14:7713-25 pubmed
    ..Therefore, both the mouse and the human TNF genes are tandemly arranged and located on the same chromosome as the MHC. ..
  30. Chin R, Lo J, Kim O, Blink S, Christiansen P, Peterson P, et al. Lymphotoxin pathway directs thymic Aire expression. Nat Immunol. 2003;4:1121-7 pubmed
    ..These findings define the essential cross-talk between thymocytes and thymic stroma that is required for central tolerance. ..
  31. Rennert P, Hochman P, Flavell R, Chaplin D, Jayaraman S, Browning J, et al. Essential role of lymph nodes in contact hypersensitivity revealed in lymphotoxin-alpha-deficient mice. J Exp Med. 2001;193:1227-38 pubmed
  32. Pasparakis M, Kousteni S, Peschon J, Kollias G. Tumor necrosis factor and the p55TNF receptor are required for optimal development of the marginal sinus and for migration of follicular dendritic cell precursors into splenic follicles. Cell Immunol. 2000;201:33-41 pubmed
  33. Muller U, Jongeneel C, Nedospasov S, Lindahl K, Steinmetz M. Tumour necrosis factor and lymphotoxin genes map close to H-2D in the mouse major histocompatibility complex. Nature. 1987;325:265-7 pubmed
    ..Initially, we mapped the TNF genes the D or Qa region in the distal half of the mouse MHC. We then studied a gene cluster encompassing part of the D and Qa regions and found the TNF genes are located 70 kb proximal to the D gene. ..
  34. Matsumoto M, Mariathasan S, Nahm M, Baranyay F, Peschon J, Chaplin D. Role of lymphotoxin and the type I TNF receptor in the formation of germinal centers. Science. 1996;271:1289-91 pubmed
    ..Germinal center formation was restored in LT-alpha-deficient mice by transplantation of normal bone marrow, indicating that the LT-alpha-expressing cells required to establish this lymphoid structure are derived from bone marrow. ..
  35. Ngo V, Korner H, Gunn M, Schmidt K, Riminton D, Cooper M, et al. Lymphotoxin alpha/beta 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. 1999;189:403-12 pubmed
    ..Here we report that BLC expression by follicular stromal cells is defective in TNF-, TNF receptor 1 (TNFR1)-, LTalpha- and LTbeta-deficient mice...
  36. Millet I, Ruddle N. Differential regulation of lymphotoxin (LT), lymphotoxin-beta (LT-beta), and TNF-alpha in murine T cell clones activated through the TCR. J Immunol. 1994;152:4336-46 pubmed
    ..These differences suggest that the reason for the redundancy of LT, LT-beta, and TNF-alpha is their differential regulation rather than their functions. ..
  37. Ansel K, Ngo V, Hyman P, Luther S, Forster R, Sedgwick J, et al. A chemokine-driven positive feedback loop organizes lymphoid follicles. Nature. 2000;406:309-14 pubmed
    ..In germinal centres the feedback loop is overridden, with B-cell lymphotoxin alpha1beta2 expression being induced by a mechanism independent of BLC. ..
  38. Berger D, Naniche D, Crowley M, Koni P, Flavell R, Oldstone M. Lymphotoxin-beta-deficient mice show defective antiviral immunity. Virology. 1999;260:136-47 pubmed
    ..These data indicate that the absence of LTbeta does not affect the intrinsic function of T lymphocytes or of dendritic cells but that the structural integrity of the spleen is strongly associated with generation of antiviral immunity. ..
  39. Kang H, Blink S, Chin R, Lee Y, Kim O, Weinstock J, et al. Lymphotoxin is required for maintaining physiological levels of serum IgE that minimizes Th1-mediated airway inflammation. J Exp Med. 2003;198:1643-52 pubmed
    ..Lymphotoxin-deficient alpha (LTalpha-/-) mice exhibit increased airway inflammation, paradoxically accompanied by diminished levels of IgE and reduced ..
  40. Lund F, Partida Sanchez S, Lee B, Kusser K, Hartson L, Hogan R, et al. Lymphotoxin-alpha-deficient mice make delayed, but effective, T and B cell responses to influenza. J Immunol. 2002;169:5236-43 pubmed
    Lymphotoxin-alpha(-/-) (LTalpha(-/-)) mice are thought to be unable to generate effective T and B cell responses. This is attributed to the lack of lymph nodes and the disrupted splenic architecture of these mice...
  41. Rangel Moreno J, Moyron Quiroz J, Carragher D, Kusser K, Hartson L, Moquin A, et al. Omental milky spots develop in the absence of lymphoid tissue-inducer cells and support B and T cell responses to peritoneal antigens. Immunity. 2009;30:731-43 pubmed publisher
    ..These results indicate that the milky spots of the omentum function as unique secondary lymphoid organs that promote immunity to peritoneal antigens...
  42. Nagatake T, Fukuyama S, Kim D, Goda K, Igarashi O, Sato S, et al. Id2-, RORgammat-, and LTbetaR-independent initiation of lymphoid organogenesis in ocular immunity. J Exp Med. 2009;206:2351-64 pubmed publisher
    ..Thus, TALT shares immunological features with MALT but has a distinct tissue genesis mechanism and plays a key role in ocular immunity. ..
  43. Kim M, McConnell F, Gaspal F, White A, Glanville S, Bekiaris V, et al. Function of CD4+CD3- cells in relation to B- and T-zone stroma in spleen. Blood. 2007;109:1602-10 pubmed
    ..CD4+CD3- cells express high levels of LTalpha, LTbeta, and tumor necrosis factor (TNF) alpha, which are the ligands for the LTbeta receptor and TNFR1 expressed ..
  44. Alimzhanov M, Kuprash D, Kosco Vilbois M, Luz A, Turetskaya R, Tarakhovsky A, et al. Abnormal development of secondary lymphoid tissues in lymphotoxin beta-deficient mice. Proc Natl Acad Sci U S A. 1997;94:9302-7 pubmed
    ..LTbeta form heterotrimers that are expressed on the surface of activated lymphocytes and natural killer cells; LTalpha homotrimers can be secreted as well...
  45. Li C, Gray P, Lin P, McGrath K, Ruddle F, Ruddle N. Cloning and expression of murine lymphotoxin cDNA. J Immunol. 1987;138:4496-501 pubmed
    ..The cDNA was transcribed and was translated in vitro, and was expressed in COS-1 cells. This has resulted in the production of LT biological activity. ..
  46. F├╝tterer A, Mink K, Luz A, Kosco Vilbois M, Pfeffer K. The lymphotoxin beta receptor controls organogenesis and affinity maturation in peripheral lymphoid tissues. Immunity. 1998;9:59-70 pubmed
    ..Since LTbetaR-/- mice exhibit distinct defects when compared to LTalpha-/- and LTbeta-/- mice, it is suggested that the LTbetaR integrates signals from other TNF family members...
  47. Korner H, Cook M, Riminton D, Lemckert F, Hoek R, Ledermann B, et al. Distinct roles for lymphotoxin-alpha and tumor necrosis factor in organogenesis and spatial organization of lymphoid tissue. Eur J Immunol. 1997;27:2600-9 pubmed
    ..for the pro-inflammatory cytokines tumor necrosis factor (TNF) and lymphotoxin (LT) were characterized in TNF/LT alpha -/- and TNF -/- mice established by direct gene targeting of C57BL/6 ES cells...
  48. Fu Y, Huang G, Wang Y, Chaplin D. Lymphotoxin-alpha-dependent spleen microenvironment supports the generation of memory B cells and is required for their subsequent antigen-induced activation. J Immunol. 2000;164:2508-14 pubmed
    b>Lymphotoxin alpha-deficient (LTalpha-/-) mice show dramatically reduced IgG responses after either primary or secondary immunizations with sheep red blood cells (SRBC)...
  49. Cariappa A, Chase C, Liu H, Russell P, Pillai S. Naive recirculating B cells mature simultaneously in the spleen and bone marrow. Blood. 2007;109:2339-45 pubmed
    ..B-cell maturation in the bone marrow was obtained from analyses of transitional B cells in splenectomized lymphotoxin alpha-deficient mice that lack all secondary lymphoid organs...
  50. Korner H, Sedgwick J. Tumour necrosis factor and lymphotoxin: molecular aspects and role in tissue-specific autoimmunity. Immunol Cell Biol. 1996;74:465-72 pubmed
  51. Pfeffer K, Matsuyama T, Kundig T, Wakeham A, Kishihara K, Shahinian A, et al. Mice deficient for the 55 kd tumor necrosis factor receptor are resistant to endotoxic shock, yet succumb to L. monocytogenes infection. Cell. 1993;73:457-67 pubmed
    ..In contrast, TNFRp55-deficient mice are severely impaired to clear L. monocytogenes and readily succumb to infection. Thus, the 55 kd TNFR plays a decisive role in the host's defense against microorganisms and their pathogenic factors. ..
  52. Lawton P, Nelson J, Tizard R, Browning J. Characterization of the mouse lymphotoxin-beta gene. J Immunol. 1995;154:239-46 pubmed
    ..Northern analysis showed that this gene is expressed predominantly in lymphoid organs. The outlining of the complete mouse TNF locus will further studies of the relationship between these genes and immune function. ..
  53. Eugster H, Muller M, Karrer U, Car B, Schnyder B, Eng V, et al. Multiple immune abnormalities in tumor necrosis factor and lymphotoxin-alpha double-deficient mice. Int Immunol. 1996;8:23-36 pubmed
    ..factor (TNF) and lymphotoxin (LT)-alpha in the development and function of the immune system, the Tnf and Ltalpha genes were simultaneously inactivated in mice by homologous recombination...
  54. Luther S, Lopez T, Bai W, Hanahan D, Cyster J. BLC expression in pancreatic islets causes B cell recruitment and lymphotoxin-dependent lymphoid neogenesis. Immunity. 2000;12:471-81 pubmed
    ..These findings establish that BLC is sufficient to activate a pathway of events leading to formation of organized lymphoid tissue. ..
  55. Sean Riminton D, Korner H, Strickland D, Lemckert F, Pollard J, Sedgwick J. 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. 1998;187:1517-28 pubmed
    ..The contribution of LT to experimental autoimmune encephalomyelitis (EAE) was examined using TNF/LTalpha-/- mice, TNF-/- mice, and a new LTalpha-/- line described here...
  56. Chiang E, Kolumam G, Yu X, Francesco M, Ivelja S, Peng I, et al. Targeted depletion of lymphotoxin-alpha-expressing TH1 and TH17 cells inhibits autoimmune disease. Nat Med. 2009;15:766-73 pubmed publisher
    ..These data indicate that depleting LT-alpha-expressing lymphocytes with LT-alpha-specific mAb may be beneficial in the treatment of autoimmune disease. ..
  57. Matsumoto M, Fu Y, Molina H, Huang G, Kim J, Thomas D, et al. Distinct roles of lymphotoxin alpha and the type I tumor necrosis factor (TNF) receptor in the establishment of follicular dendritic cells from non-bone marrow-derived cells. J Exp Med. 1997;186:1997-2004 pubmed
    In mice deficient in either lymphotoxin alpha (LT-alpha) or type I tumor necrosis factor receptor (TNFR-I), organized clusters of follicular dendritic cells (FDC) and germinal centers (GC) are absent from the spleen...
  58. Ruddle N. Lymphoid neo-organogenesis: lymphotoxin's role in inflammation and development. Immunol Res. 1999;19:119-25 pubmed
  59. Roach D, Briscoe H, Saunders B, France M, Riminton S, Britton W. Secreted lymphotoxin-alpha is essential for the control of an intracellular bacterial infection. J Exp Med. 2001;193:239-46 pubmed
    ..To overcome the lack of peripheral lymph nodes in LTalpha-/- and LTbeta-/- mice, bone marrow chimeric mice were constructed...
  60. Fu Y, Huang G, Matsumoto M, Molina H, Chaplin D. Independent signals regulate development of primary and secondary follicle structure in spleen and mesenteric lymph node. Proc Natl Acad Sci U S A. 1997;94:5739-43 pubmed
    ..These data demonstrate that the signals that regulate the development of distinct T and B cell zones as well as the signals that regulate B cell activation to produce clusters of PNA+ cells differ between the spleen and LNs. ..
  61. Togbe D, Schofield L, Grau G, Schnyder B, Boissay V, Charron S, et al. Murine cerebral malaria development is independent of toll-like receptor signaling. Am J Pathol. 2007;170:1640-8 pubmed
    ..In contrast to lymphotoxin alpha-deficient mice, which are resistant to CM, all TLR-deficient mice were as sensitive to fatal CM development ..
  62. Ryffel B, Di Padova F, Schreier M, Le Hir M, Eugster H, Quesniaux V. Lack of type 2 T cell-independent B cell responses and defect in isotype switching in TNF-lymphotoxin alpha-deficient mice. J Immunol. 1997;158:2126-33 pubmed
    ..Our previous studies had shown that TNF-LT alpha double-deficient mice have defective IgM and IgG primary Ab responses to the T cell-dependent (TD) Ag SRBC...
  63. Koni P, Sacca R, Lawton P, Browning J, Ruddle N, Flavell R. Distinct roles in lymphoid organogenesis for lymphotoxins alpha and beta revealed in lymphotoxin beta-deficient mice. Immunity. 1997;6:491-500 pubmed
    b>Lymphotoxin alpha (LT alpha)-deficient mice revealed critical roles for LT alpha in lymphoid organogenesis, but it is not clear whether LT alpha functions through an LT alpha homotrimer (LT alpha3) or LT alpha/beta heterotrimers...
  64. Taylor R, Lugering A, Newell K, Williams I. Intestinal cryptopatch formation in mice requires lymphotoxin alpha and the lymphotoxin beta receptor. J Immunol. 2004;173:7183-9 pubmed
    ..In this study, we assessed the contributions of LTalpha and LTbetaR to the development of cryptopatches (CP), aggregates of T cell precursors in the mouse small ..
  65. Banks T, Rouse B, Kerley M, Blair P, Godfrey V, Kuklin N, et al. Lymphotoxin-alpha-deficient mice. Effects on secondary lymphoid organ development and humoral immune responsiveness. J Immunol. 1995;155:1685-93 pubmed
    ..These data illustrate the utility of this mouse model as a system for understanding lymphoid organ development and its effects on immune responsiveness. ..
  66. Fu Y, Huang G, Wang Y, Chaplin D. B lymphocytes induce the formation of follicular dendritic cell clusters in a lymphotoxin alpha-dependent fashion. J Exp Med. 1998;187:1009-18 pubmed
    ..dendritic cell (FDC) clusters and germinal centers (GCs) are absent from the peripheral lymphoid tissues of LTalpha-deficient (LTalpha-/-) mice...
  67. van de Pavert S, Olivier B, Goverse G, Vondenhoff M, Greuter M, Beke P, et al. Chemokine CXCL13 is essential for lymph node initiation and is induced by retinoic acid and neuronal stimulation. Nat Immunol. 2009;10:1193-9 pubmed publisher
    ..Therefore, our data show that the initiation of lymph node development is controlled by RA-mediated expression of CXCL13 and suggest that RA may be provided by adjacent neurons. ..
  68. Rossi S, Kim M, Leibbrandt A, Parnell S, Jenkinson W, Glanville S, et al. RANK signals from CD4(+)3(-) inducer cells regulate development of Aire-expressing epithelial cells in the thymic medulla. J Exp Med. 2007;204:1267-72 pubmed
    ..Collectively, our data reveal cellular and molecular mechanisms leading to the generation of Aire(+) mTECs and highlight a previously unrecognized role for CD4(+)3(-)RANKL(+) inducer cells in intrathymic self-tolerance. ..
  69. Hamada H, Hiroi T, Nishiyama Y, Takahashi H, Masunaga Y, Hachimura S, et al. Identification of multiple isolated lymphoid follicles on the antimesenteric wall of the mouse small intestine. J Immunol. 2002;168:57-64 pubmed
    ..Neither ILF nor PP are detectable in lymphotoxin alpha(-/-) and aly/aly mice that retain well-developed cryptopatches (CP) and thymus-independent subsets of ..
  70. Rennert P, James D, Mackay F, Browning J, Hochman P. Lymph node genesis is induced by signaling through the lymphotoxin beta receptor. Immunity. 1998;9:71-9 pubmed
    ..Lymph nodes developed in LTalpha-/- mice treated in utero with agonist anti-LTbeta-R monoclonal antibody...
  71. Yamamoto M, Rennert P, McGhee J, Kweon M, Yamamoto S, Dohi T, et al. Alternate mucosal immune system: organized Peyer's patches are not required for IgA responses in the gastrointestinal tract. J Immunol. 2000;164:5184-91 pubmed
    ..Further, organized Peyer's patches are not a strict requirement for induction of mucosal IgA Ab responses in the gastrointestinal tract. ..
  72. Ying X, Chan K, Shenoy P, Hill M, Ruddle N. Lymphotoxin plays a crucial role in the development and function of nasal-associated lymphoid tissue through regulation of chemokines and peripheral node addressin. Am J Pathol. 2005;166:135-46 pubmed
  73. Rudin W, Eugster H, Bordmann G, Bonato J, Muller M, Yamage M, et al. 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. 1997;150:257-66 pubmed
    ..In the absence of TNF, ICAM-1 and nitric oxide up-regulation are reduced, and PbA infection fails to cause fatal CM. ..