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.
| Original language | English |
|---|---|
| Pages (from-to) | 1467-78 |
| Number of pages | 12 |
| Journal | Journal of Experimental Medicine |
| Volume | 192 |
| Issue number | 10 |
| Publication status | Published - 20 Nov 2000 |
Keywords
- Animals
- B-Lymphocytes
- CD3 Complex
- CD4 Antigens
- Carrier Proteins/metabolism
- Leukocyte Common Antigens
- Lymph Nodes/growth & development
- Membrane Glycoproteins/metabolism
- Mice
- Mice, Transgenic
- RANK Ligand
- Receptor Activator of Nuclear Factor-kappa B
- Spleen
- Tumor Necrosis Factor-alpha/metabolism