The Journal of Experimental Medicine
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Published online 20 November 2000.
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© The Rockefeller University Press, 0022-1007/2000/11/1467/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 10, November 20, 2000 1467-1478

Original Article

Regulation of Peripheral Lymph Node Genesis by the Tumor Necrosis Factor Family Member Trance

Dongku Kima, Reina E. Mebiusc, John D. MacMickingb, Steffen Jungd, Tom Cupedoc, Yaneth Castellanosb, Jaerang Rhoa,b, Brian R. Wonga, Regis Josiene, Nacksung Kima, Paul D. Rennertf, and Yongwon Choia,b

a Laboratory of Immunology, The Rockefeller University, New York, New York 10021
b Howard Hughes Medical Institute, The Rockefeller University, New York, New York 10021
c Department of Cell Biology and Immunology, Faculty of Medicine, Vrije Universiteit, 1081 BT Amsterdam, Netherlands
d Skirball Institute of Biomolecular Medicine, New York University Medical Center, New York, New York 10016
e Service de Néphrologie-Immunologie Clinique, CHRU de Nantes, Immeuble Jean Monnet, 44035 Nantes Cedex 1, France
f Biogen Incorporated, Cambridge, Massachusetts 02142
The Rockefeller University, Box 294, 1230 York Ave., New York, NY 10021.212-327-7319212-327-7441

Proper lymph node (LN) development requires tumor necrosis factor–related activation-induced cytokine (TRANCE) expression. Here we demonstrate that the defective LN development in TRANCE–/– mice correlates with a significant reduction in lymphotoxin (LT){alpha}β+{alpha}4β7+CD45+CD4+CD3– cells and their failure to form clusters in rudimentary mesenteric LNs. Transgenic TRANCE overexpression in TRANCE–/– mice results in selective restoration of this cell population into clusters, and results in full LN development. Transgenic TRANCE-mediated restoration of LN development requires LT{alpha}β expression on CD45+ CD4+CD3– cells, as LNs could not be induced in LT{alpha}–/– mice. LT{alpha}–/– mice also showed defects in the fate of CD45+CD4+CD3– cells similar to TRANCE–/– mice. Thus, we propose that both TRANCE and LT{alpha}β regulate the colonization and cluster formation by CD45+ CD4+CD3– cells in developing LNs, the degree of which appears to correlate with the state of LN organogenesis.

Key Words: TRANCE • lymphotoxin • tumor necrosis factor • lymph node • organogenesis

Abbreviations used in this paper: CLN, cervical LN; GC, germinal center; HPRT, 5'-hypoxanthine ribosyltransferase; LT, lymphotoxin; MAdCAM, mucosal addressin cell adhesion molecule; MLN, mesenteric LN; PLN, peripheral LN; PP, Peyer's patch; rMLN; rudiments of MLN; TRANCE, TNF-related activation-induced cytokine; WT, wild-type.

D. Kim and R.E. Mebius contributed equally to this work.

© 2000 The Rockefeller University Press


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