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The requirement of membrane lymphotoxin for the presence of dendritic cells in lymphoid tissues.

Wu Q, Wang Y, Wang J, Hedgeman EO, Browning JL, Fu YX - J. Exp. Med. (1999)

Bottom Line: Although several cytokines, including tumor necrosis factor (TNF), can promote the growth of dendritic cells (DCs) in vitro, the cytokines that naturally regulate DC development and function in vivo have not been well defined.These data suggest that membrane LT is an essential ligand for the presence of DCs in the spleen.Taken together, these results support the notion that the signaling via LTbetaR by membrane LTalpha/beta is required for the presence of DCs in lymphoid tissues.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, The University of Chicago, Chicago, Illinois 60637, USA.

ABSTRACT
Although several cytokines, including tumor necrosis factor (TNF), can promote the growth of dendritic cells (DCs) in vitro, the cytokines that naturally regulate DC development and function in vivo have not been well defined. Here, we report that membrane lymphotoxin (LT), instead of TNF, regulates the migration of DCs in the spleen. LTalpha(-/-) mice, lacking membrane LTalpha/beta and LTalpha(3), show markedly reduced numbers of DCs in the spleen. Unlike wild-type mice and TNF(-/-) mice that have densely clustered DCs in the T cell zone and around the marginal zone, splenic DCs in LTalpha(-/-) mice are randomly distributed. The reduced number of DCs in lymphoid tissues of LTalpha(-/-) mice is associated with an increased number of DCs in nonlymphoid tissues. The number of splenic DCs in LTalpha(-/-) mice is restored when additional LT-expressing cells are provided. Blocking membrane LTalpha/beta in wild-type mice markedly diminishes the accumulation of DCs in lymphoid tissues. These data suggest that membrane LT is an essential ligand for the presence of DCs in the spleen. Mice deficient in TNF receptor, which is the receptor for both soluble LTalpha(3) and TNF-alpha(3) trimers, have normal numbers of DCs. However, LTbetaR(-/-) mice show reduced numbers of DCs, similar to the mice lacking membrane LT alpha/beta. Taken together, these results support the notion that the signaling via LTbetaR by membrane LTalpha/beta is required for the presence of DCs in lymphoid tissues.

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Determination of the distribution of splenic DCs by BM-derived cells in an LT-dependent fashion. BM reconstitution was performed according to previously described methods 12. 6 wk after BM reconstitution, spleens were collected and treated by using collagenase 24. The cells were stained for anti-CD11c and anti–class II antibody. Data from one of three experiments is presented.
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Figure 5: Determination of the distribution of splenic DCs by BM-derived cells in an LT-dependent fashion. BM reconstitution was performed according to previously described methods 12. 6 wk after BM reconstitution, spleens were collected and treated by using collagenase 24. The cells were stained for anti-CD11c and anti–class II antibody. Data from one of three experiments is presented.

Mentions: BM transfer in long-term reconstitution provides a model to evaluate the role of LTα in determination of the splenic microenvironment that permits the migration of DCs. 6 wk after lethally irradiated LTα−/− mice were reconstituted with wt BM, DCs were restored to a level similar to that seen in irradiated wt mice reconstituted with wt BM (Fig. 5). This suggests that the altered microenvironment that impairs the migration of DCs is not developmentally fixed and that LT-expressing BM cells could restore the migration of DCs. In contrast, when lethally irradiated wt mice were reconstituted with LTα−/− BM, the number of DCs in the spleen was reduced, as is seen in LTα−/− mice or LTβR–Ig-treated mice (Fig. 5). Therefore, the LTα-mediated microenvironment that permits the migration of DCs is primarily determined and maintained by LT-expressing BM-derived cells.


The requirement of membrane lymphotoxin for the presence of dendritic cells in lymphoid tissues.

Wu Q, Wang Y, Wang J, Hedgeman EO, Browning JL, Fu YX - J. Exp. Med. (1999)

Determination of the distribution of splenic DCs by BM-derived cells in an LT-dependent fashion. BM reconstitution was performed according to previously described methods 12. 6 wk after BM reconstitution, spleens were collected and treated by using collagenase 24. The cells were stained for anti-CD11c and anti–class II antibody. Data from one of three experiments is presented.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2195624&req=5

Figure 5: Determination of the distribution of splenic DCs by BM-derived cells in an LT-dependent fashion. BM reconstitution was performed according to previously described methods 12. 6 wk after BM reconstitution, spleens were collected and treated by using collagenase 24. The cells were stained for anti-CD11c and anti–class II antibody. Data from one of three experiments is presented.
Mentions: BM transfer in long-term reconstitution provides a model to evaluate the role of LTα in determination of the splenic microenvironment that permits the migration of DCs. 6 wk after lethally irradiated LTα−/− mice were reconstituted with wt BM, DCs were restored to a level similar to that seen in irradiated wt mice reconstituted with wt BM (Fig. 5). This suggests that the altered microenvironment that impairs the migration of DCs is not developmentally fixed and that LT-expressing BM cells could restore the migration of DCs. In contrast, when lethally irradiated wt mice were reconstituted with LTα−/− BM, the number of DCs in the spleen was reduced, as is seen in LTα−/− mice or LTβR–Ig-treated mice (Fig. 5). Therefore, the LTα-mediated microenvironment that permits the migration of DCs is primarily determined and maintained by LT-expressing BM-derived cells.

Bottom Line: Although several cytokines, including tumor necrosis factor (TNF), can promote the growth of dendritic cells (DCs) in vitro, the cytokines that naturally regulate DC development and function in vivo have not been well defined.These data suggest that membrane LT is an essential ligand for the presence of DCs in the spleen.Taken together, these results support the notion that the signaling via LTbetaR by membrane LTalpha/beta is required for the presence of DCs in lymphoid tissues.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, The University of Chicago, Chicago, Illinois 60637, USA.

ABSTRACT
Although several cytokines, including tumor necrosis factor (TNF), can promote the growth of dendritic cells (DCs) in vitro, the cytokines that naturally regulate DC development and function in vivo have not been well defined. Here, we report that membrane lymphotoxin (LT), instead of TNF, regulates the migration of DCs in the spleen. LTalpha(-/-) mice, lacking membrane LTalpha/beta and LTalpha(3), show markedly reduced numbers of DCs in the spleen. Unlike wild-type mice and TNF(-/-) mice that have densely clustered DCs in the T cell zone and around the marginal zone, splenic DCs in LTalpha(-/-) mice are randomly distributed. The reduced number of DCs in lymphoid tissues of LTalpha(-/-) mice is associated with an increased number of DCs in nonlymphoid tissues. The number of splenic DCs in LTalpha(-/-) mice is restored when additional LT-expressing cells are provided. Blocking membrane LTalpha/beta in wild-type mice markedly diminishes the accumulation of DCs in lymphoid tissues. These data suggest that membrane LT is an essential ligand for the presence of DCs in the spleen. Mice deficient in TNF receptor, which is the receptor for both soluble LTalpha(3) and TNF-alpha(3) trimers, have normal numbers of DCs. However, LTbetaR(-/-) mice show reduced numbers of DCs, similar to the mice lacking membrane LT alpha/beta. Taken together, these results support the notion that the signaling via LTbetaR by membrane LTalpha/beta is required for the presence of DCs in lymphoid tissues.

Show MeSH
Related in: MedlinePlus