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

doi:10.1084/jem.192.10.1467

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 Kim^a, Reina E. Mebius^c, John D. MacMicking^b, Steffen Jung^d, Tom Cupedo^c, Yaneth Castellanos^b, Jaerang Rho^a,b, Brian R. Wong^a, Regis Josien^e, Nacksung Kim^a, Paul D. Rennert^f, and Yongwon Choi^a,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

Correspondence to: Yongwon Choi, The Rockefeller University, Box 294, 1230 York Ave., New York, NY 10021. Tel:212-327-7441 Fax:212-327-7319

Proper lymph node (LN) development requires tumor necrosis factor–relatedactivation-induced cytokine (TRANCE) expression. Here we demonstratethat the defective LN development in TRANCE^-/- mice correlateswith a significant reduction in lymphotoxin (LT) ${alpha}$ ß⁺ ${alpha}$ ₄ß₇⁺CD45⁺CD4⁺CD3^-cells and their failure to form clusters in rudimentary mesentericLNs. Transgenic TRANCE overexpression in TRANCE^-/- mice resultsin selective restoration of this cell population into clusters,and results in full LN development. Transgenic TRANCE-mediatedrestoration of LN development requires LT ${alpha}$ ß expressionon 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 bothTRANCE and LT ${alpha}$ ß regulate the colonization and clusterformation by CD45⁺ CD4⁺CD3^- cells in developing LNs, the degreeof which appears to correlate with the state of LN organogenesis.

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

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