Abnormal Development of Peripheral Lymphoid Organs in Mice Deficient in Lymphotoxin

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.

The unexpected role of lymphotoxin β receptor signaling in carcinogenesis: from lymphoid tissue formation to liver and prostate cancer development

“…LTa À/À , LTb À/À and LTbR À/À mice display severe developmental defects in lymph node and Peyer's patch neogenesis, a disorganized lymphoid microarchitecture and lack of mature follicular dendritic cells (Pfeffer et al, 1993;De Togni et al, 1994;Koni et al, 1997;Futterer et al, 1998;Ngo et al, 1999). In addition, LTa À/À and LTbR À/À mice show inflammatory disorders in nonlymphoid organs (for example, lung, liver, kidney; (Fu et al, 1997(Fu et al, , 2000Fu and Chaplin, 1999;Chin et al, 2003).…”

Family-based analysis of tumor necrosis factor and lymphotoxin-α tag polymorphisms with type 1 diabetes in the population of South Croatia

“…The LTA cytokine is produced by lymphocytes and mediates a large number of inflammatory, immunostimulatory and antiviral responses [6]. The role of LTA was demonstrated as essential for the normal development of peripheral lymphoid organs in mice models [14]. It was shown that administration of LTA in NOD mice and Bio-Breeding (BB) rats may have modulated autoimmunity and prevented development of T1DM [15].…”

Lymphotoxin-α is an autocrine growth factor for chronic lymphocytic leukemia B cells

“…8 Studies of natural functions of LT by production of an LT-deficient mouse strain suggest an essential role for LT in the normal development of peripheral lymphoid organs. 9 Mice deficient in LT have no morphologically detectable lymph nodes or Peyer's patches, although the thymus appears to be normal. Within the white pulp of the spleen, there is a failure of normal segregation of B and T cells, and lymphocytes positive for immunoglobulin M are present in increased numbers in both the spleen and peripheral blood.…”

“…Within the white pulp of the spleen, there is a failure of normal segregation of B and T cells, and lymphocytes positive for immunoglobulin M are present in increased numbers in both the spleen and peripheral blood. 9 Moreover, LT has been found to be an autocrine growth factor for EBV-infected B cell lines. 10 In this report we analyzed the potential role of LT in CLL, a low-grade B cell malignancy.…”