Abnormal Development of Peripheral Lymphoid Organs in Mice Deficient in Lymphotoxin

Yale University, New Haven, Connecticut, United States
Science (Impact Factor: 33.61). 05/1994; 264(5159):703-7. DOI: 10.1126/science.8171322
Source: PubMed


Mice rendered deficient in lymphotoxin (LT) by gene targeting in embryonic stem cells have no morphologically detectable lymph
nodes or Peyer's patches, although development of the thymus appears normal. Within the white pulp of the spleen, there is
failure of normal segregation of B and T cells. Spleen and peripheral blood contain CD4+CD8- and CD4-CD8+ T cells in a normal
ratio, and both T cells subsets have an apparently normal lytic function. Lymphocytes positive for immunoglobulin M are present
in increased numbers in both the spleen and peripheral blood. These data suggest an essential role for LT in the normal development
of peripheral lymphoid organs.

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    • "Muc1 [22], [23], matrix metalloproteinase 13 (MMP13) [24], and the extracellular matrix proteins decorin and dermatopontin [25] produce protective mucus. Lymphotoxin-beta (Ltb) is a molecule related to signaling in stromal cells to produce factors that organize lymphoid cells into lymph nodes [26]. The transcription of Reg3γ is involved in tissue repair and antimicrobial responses [27]. "
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    PLoS ONE 09/2014; 9(9):e106807. DOI:10.1371/journal.pone.0106807 · 3.23 Impact Factor
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    • "LECs are therefore necessary for LN development as they contribute to the further increase of LTi numbers, after the initial clustering of LTi resulting in normal-sized clusters of LTi and LTo cells. Conversely, lymphatic vasculature formation can occur without the presence of lymph nodes as various mouse models devoid of lymph nodes, such as RORc À/À or the LTα À/À , contain lymphatic vessels (Sun et al. 2000; De Togni et al. 1994). "
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    Advances in anatomy, embryology, and cell biology 01/2014; 214:81-91. DOI:10.1007/978-3-7091-1646-3_7 · 17.00 Impact Factor
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    • "Rotavirus induces specific IgA antibody in the PP and this precedes appearance of IgA in the lamina propria (101), suggestive that rotavirus-specific antibodies originate in the PP and not the lamina propria. This is supported by studies in mice that lack expression of the TNF family member LTα that do not develop Peyer’s patches (203) and these mice are unable to clear rotavirus infection or produce stool rotavirus-specific IgA following virus exposure (204). This is similar to the response seen in B cell, IgA, and J-chain knockout animals (140, 179, 194, 197). "
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    ABSTRACT: Viral gastroenteritis is one of the leading causes of diseases that kill ~2.2 million people worldwide each year. IgA is one of the major immune effector products present in the gastrointestinal tract yet its importance in protection against gastrointestinal viral infections has been difficult to prove. In part this has been due to a lack of small and large animal models in which pathogenesis of and immunity to gastrointestinal viral infections is similar to that in humans. Much of what we have learned about the role of IgA in the intestinal immune response has been obtained from experimental animal models of rotavirus infection. Rotavirus-specific intestinal IgA appears to be one of the principle effectors of long term protection against rotavirus infection. Thus, there has been a focus on understanding the immunological pathways through which this virus-specific IgA is induced during infection. In addition, the experimental animal models of rotavirus infection provide excellent systems in which new areas of research on viral-specific intestinal IgA including the long term maintenance of viral-specific IgA.
    Frontiers in Immunology 11/2013; 4:402. DOI:10.3389/fimmu.2013.00402
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