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Regulation of peripheral lymph node genesis by the tumor necrosis factor family member TRANCE.

Kim D, Mebius RE, MacMicking JD, Jung S, Cupedo T, Castellanos Y, Rho J, Wong BR, Josien R, Kim N, Rennert PD, Choi Y - J. Exp. Med. (2000)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Immunology, The Rockefeller University, New York, New York 10021, USA.

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.

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Generation of TRANCE−/− mice: a gene dosage effect on TRANCE expression. (A) Reverse transcription PCR analysis of thymocytes or activated CD8+ T cells from WT, TRANCE+/−, and TRANCE−/− mice. TRANCE-R mRNA expression was also examined and HPRT served as an internal control. (B) Flow cytometric analysis of activated CD8+ T cells from WT, TRANCE+/−, and TRANCE−/− mice. Cells were stained with hIgG1 (gray lines) or TRANCE-R-IgG1 (thick lines) followed by PE-coupled goat anti–human IgG1.
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Figure 1: Generation of TRANCE−/− mice: a gene dosage effect on TRANCE expression. (A) Reverse transcription PCR analysis of thymocytes or activated CD8+ T cells from WT, TRANCE+/−, and TRANCE−/− mice. TRANCE-R mRNA expression was also examined and HPRT served as an internal control. (B) Flow cytometric analysis of activated CD8+ T cells from WT, TRANCE+/−, and TRANCE−/− mice. Cells were stained with hIgG1 (gray lines) or TRANCE-R-IgG1 (thick lines) followed by PE-coupled goat anti–human IgG1.

Mentions: TRANCE−/− mice were described as having a defect in LN organogenesis but not in PP development or maintenance of splenic architecture 17. To further study the role of TRANCE in LN genesis, we have generated TRANCE−/− mice by homologous recombination, in which nucelotides 699–1089 of exon 5 (amino acids 185–316) plus the additional 1123-bp 3′ untranslated region have been deleted (data not shown). The overall phenotype of our TRANCE−/− mice was essentially similar to that described 17 such that TRANCE−/− mice failed to develop PLNs and MLNs (see below) and osteoclasts (data not shown). Of note, however, we showed here that TRANCE+/− mice displayed intermediate levels of TRANCE expression (Fig. 1), indicating a gene dosage effect.


Regulation of peripheral lymph node genesis by the tumor necrosis factor family member TRANCE.

Kim D, Mebius RE, MacMicking JD, Jung S, Cupedo T, Castellanos Y, Rho J, Wong BR, Josien R, Kim N, Rennert PD, Choi Y - J. Exp. Med. (2000)

Generation of TRANCE−/− mice: a gene dosage effect on TRANCE expression. (A) Reverse transcription PCR analysis of thymocytes or activated CD8+ T cells from WT, TRANCE+/−, and TRANCE−/− mice. TRANCE-R mRNA expression was also examined and HPRT served as an internal control. (B) Flow cytometric analysis of activated CD8+ T cells from WT, TRANCE+/−, and TRANCE−/− mice. Cells were stained with hIgG1 (gray lines) or TRANCE-R-IgG1 (thick lines) followed by PE-coupled goat anti–human IgG1.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2193182&req=5

Figure 1: Generation of TRANCE−/− mice: a gene dosage effect on TRANCE expression. (A) Reverse transcription PCR analysis of thymocytes or activated CD8+ T cells from WT, TRANCE+/−, and TRANCE−/− mice. TRANCE-R mRNA expression was also examined and HPRT served as an internal control. (B) Flow cytometric analysis of activated CD8+ T cells from WT, TRANCE+/−, and TRANCE−/− mice. Cells were stained with hIgG1 (gray lines) or TRANCE-R-IgG1 (thick lines) followed by PE-coupled goat anti–human IgG1.
Mentions: TRANCE−/− mice were described as having a defect in LN organogenesis but not in PP development or maintenance of splenic architecture 17. To further study the role of TRANCE in LN genesis, we have generated TRANCE−/− mice by homologous recombination, in which nucelotides 699–1089 of exon 5 (amino acids 185–316) plus the additional 1123-bp 3′ untranslated region have been deleted (data not shown). The overall phenotype of our TRANCE−/− mice was essentially similar to that described 17 such that TRANCE−/− mice failed to develop PLNs and MLNs (see below) and osteoclasts (data not shown). Of note, however, we showed here that TRANCE+/− mice displayed intermediate levels of TRANCE expression (Fig. 1), indicating a gene dosage effect.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Immunology, The Rockefeller University, New York, New York 10021, USA.

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.

Show MeSH
Related in: MedlinePlus