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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    ABSTRACT: Many epidemiological studies have suggested that the recent increase in prevalence and severity of allergic diseases such as asthma is inversely correlated with Mycobacterium bovis bacillus Calmette Guerin (BCG) vaccination. However, the underlying mechanisms by which mycobacterial components suppress allergic diseases are not yet fully understood. Here we showed the inhibitory mechanisms for development of allergic airway inflammation by using highly purified recombinant Ag85B (rAg85B), which is one of the major protein antigens secreted from M. tuberculosis. Ag85B is thought to be a single immunogenic protein that can elicit a strong Th1-type immune response in hosts infected with mycobacteria, including individuals vaccinated with BCG. Administration of rAg85B showed a strong inhibitory effect on the development of allergic airway inflammation with induction of Th1-response and IL-17and IL-22 production. Both cytokines induced by rAg85B were involved in the induction of Th17-related cytokine-production innate immune cells in the lung. Administration of neutralizing antibodies to IL-17 or IL-22 in rAg85B-treated mice revealed that IL-17 induced the infiltration of neutrophils in BAL fluid and that allergen-induced bronchial eosinophilia was inhibited by IL-22. Furthermore, enhancement of the expression of genes associated with tissue homeostasis and wound healing was observed in bronchial tissues after rAg85B administration in a Th17-related cytokine dependent manner. The results of this study provide evidence for the potential usefulness of rAg85B as a novel approach for anti-allergic effect and tissue repair other than the role as a conventional TB vaccine.
    Full-text · Article · Sep 2014 · PLoS ONE
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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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    Full-text · Article · Jan 2014 · Advances in anatomy, embryology, and cell biology
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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.
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