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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

Original Article

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

Qiang Wua, Yang Wanga, Jing Wanga, Elizabeth O. Hedgemana, Jeffrey L. Browningb, and Yang-Xin Fua

a From the Department of Pathology, The University of Chicago, Chicago, Illinois 60637
b Department of Immunology and Inflammation, Biogen, Incorporated, Cambridge, Massachusetts 02142
Dept. of Pathology, MC6027, The University of Chicago, 5841 S. Maryland Ave., Chicago, IL 60637.773-702-6260773-702-0929

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 function in vivo have not been well defined. Here, we report that membrane lymphotoxin (LT), instead of TNF, regulates the migration of DCs in the spleen. LT{alpha}–/– mice, lacking membrane LT{alpha}/β and LT{alpha}3, show markedly reduced numbers of DCs in the spleen. Unlike wild-type mice and TNF–/– mice that have densely clustered DCs in the T cell zone and around the marginal zone, splenic DCs in LT{alpha}–/– mice are randomly distributed. The reduced number of DCs in lymphoid tissues of LT{alpha}–/– mice is associated with an increased number of DCs in nonlymphoid tissues. The number of splenic DCs in LT{alpha}–/– mice is restored when additional LT-expressing cells are provided. Blocking membrane LT{alpha}/β in wild-type mice markedly diminishes the accumulation of DCs in lymphoid tissues. These data suggest that membrane LT is an essential ligand for the presence of DCs in the spleen. Mice deficient in TNF receptor, which is the receptor for both soluble LT{alpha}3 and TNF-{alpha}3 trimers, have normal numbers of DCs. However, LTβR–/– mice show reduced numbers of DCs, similar to the mice lacking membrane LT {alpha}/β. Taken together, these results support the notion that the signaling via LTβR by membrane LT{alpha}/β is required for the presence of DCs in lymphoid tissues.

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

1used in this paper: BM, bone marrow; DCs, dendritic cells; FDCs, follicular dendritic cells; LT, lymphotoxin; MLR, mixed leukocyte reaction; MZs, marginal zones; wt, wild-type

© 1999 The Rockefeller University Press


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