The Requirement of Membrane Lymphotoxin for the Presence of Dendritic Cells in Lymphoid Tissues

doi:10.1084/jem.190.5.629

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© The Rockefeller University Press, 0022-1007/1999/9/629/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 5, September 6, 1999 629-638

The Requirement of Membrane Lymphotoxin for the Presence of Dendritic Cells in Lymphoid Tissues

Qiang Wu^a, Yang Wang^a, Jing Wang^a, Elizabeth O. Hedgeman^a, Jeffrey L. Browning^b, and Yang-Xin Fu^a
^a From the Department of Pathology, The University of Chicago, Chicago, Illinois 60637
^b Department of Immunology and Inflammation, Biogen, Incorporated, Cambridge, Massachusetts 02142

Correspondence to: Yang-Xin Fu, Dept. of Pathology, MC6027, The University of Chicago, 5841 S. Maryland Ave., Chicago, IL 60637. Tel:773-702-0929 Fax:773-702-6260 E-mail:yfu{at}midway.uchicago.edu.

Although several cytokines, including tumor necrosis factor(TNF), can promote the growth of dendritic cells (DCs) in vitro,the cytokines that naturally regulate DC development and functionin vivo have not been well defined. Here, we report that membranelymphotoxin (LT), instead of TNF, regulates the migration ofDCs in the spleen. LT ${alpha}$ ^-/- mice, lacking membrane LT ${alpha}$ /ß andLT ${alpha}$ ₃, show markedly reduced numbers of DCs in the spleen. Unlikewild-type mice and TNF^-/- mice that have densely clustered DCsin the T cell zone and around the marginal zone, splenic DCsin LT ${alpha}$ ^-/- mice are randomly distributed. The reduced number ofDCs in lymphoid tissues of LT ${alpha}$ ^-/- mice is associated with anincreased number of DCs in nonlymphoid tissues. The number ofsplenic DCs in LT ${alpha}$ ^-/- mice is restored when additional LT-expressingcells are provided. Blocking membrane LT ${alpha}$ /ß in wild-typemice markedly diminishes the accumulation of DCs in lymphoidtissues. These data suggest that membrane LT is an essentialligand for the presence of DCs in the spleen. Mice deficientin TNF receptor, which is the receptor for both soluble LT ${alpha}$ ₃and TNF- ${alpha}$ ₃ trimers, have normal numbers of DCs. However, LTßR^-/-mice show reduced numbers of DCs, similar to the mice lackingmembrane LT ${alpha}$ /ß. Taken together, these results supportthe notion that the signaling via LTßR by membrane LT ${alpha}$ /ßis required for the presence of DCs in lymphoid tissues.

Key Words: membrane lymphotoxin, tumor necrosis factor, dendritic cells,lymphotoxin receptor, migration

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