title: Regulation of peripheral lymph node genesis by the tumor necrosis factor family member TRANCE.
abstract: 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)alphabeta(+)alpha(4)beta(7)(+)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 LTalphabeta expression on CD45(+) CD4(+)CD3(-) cells, as LNs could not be induced in LTalpha(-/)- mice. LTalpha(-/)- mice also showed defects in the fate of CD45(+)CD4(+)CD3(-) cells similar to TRANCE(-/)- mice. Thus, we propose that both TRANCE and LTalphabeta 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.
authors.affiliation: Laboratory of Immunology, The Rockefeller University, New York, New York 10021, USA.
authors.forename: D
authors.initials: D
authors.lastname: Kim
authors.forename: R E
authors.initials: RE
authors.lastname: Mebius
authors.forename: J D
authors.initials: JD
authors.lastname: MacMicking
authors.forename: S
authors.initials: S
authors.lastname: Jung
authors.forename: T
authors.initials: T
authors.lastname: Cupedo
authors.forename: Y
authors.initials: Y
authors.lastname: Castellanos
authors.forename: J
authors.initials: J
authors.lastname: Rho
authors.forename: B R
authors.initials: BR
authors.lastname: Wong
authors.forename: R
authors.initials: R
authors.lastname: Josien
authors.forename: N
authors.initials: N
authors.lastname: Kim
authors.forename: P D
authors.initials: PD
authors.lastname: Rennert
authors.forename: Y
authors.initials: Y
authors.lastname: Choi
mesh_terms: D000818:Animals; D001402:B-Lymphocytes; D017252:CD3 Complex; D015704:CD4 Antigens; D002352:Carrier Proteins / Q000378:metabolism*; D017493:Leukocyte Common Antigens; D008198:Lymph Nodes / Q000254:growth & development*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D013154:Spleen; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D017252:CD3 Complex; D015704:CD4 Antigens; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D017493:Leukocyte Common Antigens