For more than a decade, the biological roles and the apparent redundancy of the cytokines tumor necrosis factor (TNF) and lymphotoxin (LT) have been debated. LT alpha exists in its soluble form as a homotrimer, which like TNF only binds the TNF receptors, TNF-R55 or TNF-R75. The cell surface form of LT exists as a heteromer of LT alpha and LT beta subunits and this complex specifically binds the LT beta receptor (LT beta-R). To discriminate the functions of the LT and TNF systems, soluble LT beta-R-immunoglobulin (Ig) or TNF-R-Ig fusion proteins were introduced into embryonic circulation by injecting pregnant mice. Exposure to LT beta-R-Ig during gestation disrupted lymph node development and splenic architecture in the progeny indicating that both effects are mediated by the surface LT alpha/beta complex. These data are the first to identify a cell surface ligand involved in immune organ morphogenesis. Moreover, they unambiguously discriminate the functions of the various TNF/LT ligands, provide a unique model to study compartmentalization of immune responses and illustrate the generic utility of receptor-Ig fusion proteins for dissecting/ordering ontogenetic events in the absence of genetic modifications.
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1 November 1996
Article|
November 01 1996
Surface lymphotoxin alpha/beta complex is required for the development of peripheral lymphoid organs.
P D Rennert,
P D Rennert
Biogen Inc., Cambridge, Massachusetts 02142, USA.
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J L Browning,
J L Browning
Biogen Inc., Cambridge, Massachusetts 02142, USA.
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R Mebius,
R Mebius
Biogen Inc., Cambridge, Massachusetts 02142, USA.
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F Mackay,
F Mackay
Biogen Inc., Cambridge, Massachusetts 02142, USA.
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P S Hochman
P S Hochman
Biogen Inc., Cambridge, Massachusetts 02142, USA.
Search for other works by this author on:
P D Rennert
Biogen Inc., Cambridge, Massachusetts 02142, USA.
J L Browning
Biogen Inc., Cambridge, Massachusetts 02142, USA.
R Mebius
Biogen Inc., Cambridge, Massachusetts 02142, USA.
F Mackay
Biogen Inc., Cambridge, Massachusetts 02142, USA.
P S Hochman
Biogen Inc., Cambridge, Massachusetts 02142, USA.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1996) 184 (5): 1999–2006.
Citation
P D Rennert, J L Browning, R Mebius, F Mackay, P S Hochman; Surface lymphotoxin alpha/beta complex is required for the development of peripheral lymphoid organs.. J Exp Med 1 November 1996; 184 (5): 1999–2006. doi: https://doi.org/10.1084/jem.184.5.1999
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