Regulation of peripheral lymph node genesis by the tumor necrosis factor family member TRANCE.
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.
Kim
D
D
Laboratory of Immunology, The Rockefeller University, New York, New York 10021, USA.
Mebius
R E
RE
MacMicking
J D
JD
Jung
S
S
Cupedo
T
T
Castellanos
Y
Y
Rho
J
J
Wong
B R
BR
Josien
R
R
Kim
N
N
Rennert
P D
PD
Choi
Y
Y
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*
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