Immunodeficiency of Tumor Necrosis Factor and Lymphotoxin-α Double-Deficient Mice

  • Hans-Pietro Eugster
  • Matthias Müller
  • Michel Le Hir
  • Bernhard Ryffel
Part of the Contemporary Immunology book series (CONTIM)


Tumor necrosis factor (TNF) is a iproinflammatory cytokine involved in host defense and pathogenesis of various diseases (1,2). Soluble trimeric TNF ligands bind to TNF receptor 1 (TNFR1) and TNFR2, leading to receptor homotrimer formation (3) and consecutive triggering of various biological responses such as proliferation, cytotoxicity and apoptosis in target cells. Lyrnphotoxin-α (LTα), which like TNF belongs to the family of TNF-like ligands (4), can bind to the same receptors as TNF. Consequently, administration of TNF and LTα leads to similar biological responses in vivo and in vitro. In mice, TNF is mainly expressed in macrophages and T-cells, whereas LTα expression is confined to T- and B-cells. ‘The redundancy in receptor binding and the overlapping expression pattern of TNF and LTα renders a clearcut dissection of their function rather difficult. Therefore, the importance of both ligands to TNF receptor-mediated effects tends to be obscured in single gene knockout mice, because the loss of one ligand may be compensated by the remaining one. Since both genes are very closely linked and map within the major histo compatibility complex (MHC), single mutations cannot be crossed together. Rather, mice deficient for both ligands have to be generated by simultaneous targeting of both genes. Prominent functions of TNF include central roles in endotoxic shock, host defence, and tumor—or parasite—induced cachexia. In addition TNF plays an important, yet undefined role in the pathogenesis of autoimmune diseases (5–9). LTα deficiency has been shown to lead to aberrant development of the spleen and absence of lymph nodes (LNs) (10–11). Recently a third ligand, LTβ, was cloned and characterized as present on the cell surface as a LTα/2LTβ heterotrimer, able to bind to the newly described LTβ specific receptor (12–14).


Tumor Necrosis Factor Mutant Mouse Listeria Monocytogenes Vesicular Stomatitis Virus Endotoxic Shock 
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© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Hans-Pietro Eugster
  • Matthias Müller
  • Michel Le Hir
  • Bernhard Ryffel

There are no affiliations available

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