Article

Abnormal Development of Peripheral Lymphoid Organs in Mice Deficient in Lymphotoxin

Yale University, New Haven, Connecticut, United States
Science (Impact Factor: 31.48). 05/1994; 264(5159):703-7. DOI: 10.1126/science.8171322
Source: PubMed

ABSTRACT 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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    • "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 · 9.80 Impact Factor
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    • "Gene-expression analysis revealed that these cells provide molecules involved in LN organogenesis including LTbR, RANKL, CCL19, CCL21, CXCL13, and IL-7 (Cupedo et al., 2004c; Bé né zech et al., 2010). However, neither global gene ablation of LTbRligands (De Togni et al., 1994; Koni et al., 1997) or the LTbR itself (Fü tterer et al., 1998), nor LTbR expression on mesenchymal stromal cells of the LN anlage (Cupedo et al., 2004c; White et al., 2007; Bé né zech et al., 2010) has allowed for the determination of the developmental window of LTbR-dependent mesenchymal LTo cell stimulation that is critical for LN or PP development. Deletion of genes in a cell-specific and spatiotemporally controlled manner can be achieved by utilizing the Cre-loxP system. "
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    • "Gene-expression analysis revealed that these cells provide molecules involved in LN organogenesis including LTbR, RANKL, CCL19, CCL21, CXCL13, and IL-7 (Cupedo et al., 2004c; Bé né zech et al., 2010). However, neither global gene ablation of LTbRligands (De Togni et al., 1994; Koni et al., 1997) or the LTbR itself (Fü tterer et al., 1998), nor LTbR expression on mesenchymal Immunity 38, 1–12, May 23, 2013 ª2013 Elsevier Inc. 1 Please cite this article in press as: Chai et al., Maturation of Lymph Node Fibroblastic Reticular Cells from Myofibroblastic Precursors Is Critical for Antiviral Immunity, Immunity (2013), http://dx.doi.org/10.1016/j.immuni.2013.03.012 stromal cells of the LN anlage (Cupedo et al., 2004c; White et al., 2007; Bé né zech et al., 2010) has allowed for the determination of the developmental window of LTbR-dependent mesenchymal LTo cell stimulation that is critical for LN or PP development. Deletion of genes in a cell-specific and spatiotemporally controlled manner can be achieved by utilizing the Cre-loxP system. "
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    ABSTRACT: The stromal scaffold of the lymph node (LN) paracortex is built by fibroblastic reticular cells (FRCs). Conditional ablation of lymphotoxin-β receptor (LTβR) expression in LN FRCs and their mesenchymal progenitors in developing LNs revealed that LTβR-signaling in these cells was not essential for the formation of LNs. Although T cell zone reticular cells had lost podoplanin expression, they still formed a functional conduit system and showed enhanced expression of myofibroblastic markers. However, essential immune functions of FRCs, including homeostatic chemokine and interleukin-7 expression, were impaired. These changes in T cell zone reticular cell function were associated with increased susceptibility to viral infection. Thus, myofibroblasic FRC precursors are able to generate the basic T cell zone infrastructure, whereas LTβR-dependent maturation of FRCs guarantees full immunocompetence and hence optimal LN function during infection.
    Immunity 04/2013; 38(5). DOI:10.1016/j.immuni.2013.03.012 · 19.75 Impact Factor
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