| Lymph node expansion during immune responses is accompanied by rapid vascular expansion. The maturation, or reestablishment of quiescence and stabilization of the newly expanded vasculature and the regulatory mechanisms involved have not been well studied. We showed that while initiation of vascular expansion in immune-stimulated nodes is associated with upregulated endothelial cell proliferation, increased high endothelial venule trafficking efficiency and VCAM-1 expression, and disrupted perivascular fibroblastic reticular cell organization, the reestablishment of vascular quiescence and stabilization after expansion is characterized by reversal of these phenomena. Although CD11cmed cells are associated with the initiation of vascular expansion, CD11ch'MHCIImed dendritic cells accumulate later and their short-term depletion in mice abrogates the reestablishment of vascular quiescence and stabilization. CD11chiMHCIImed cells promote endothelial cell quiescence in vitro and, in vivo, mediate quiescence at least in part by downregulating lymph node vascular endothelial growth factor (VEGF) levels. TGFbeta1 produced by CD11hiMHCIImed cells may be important for the re-establishment of vascular quiescence and stabilization. In addition, disrupted vascular quiescence and stabilization in expanded nodes is associated with attenuated T cell-dependent B cell responses, which may be due to decreased B cell activating factor (BAFF) levels in the T zone. These results describe a novel mechanism whereby CD11chiMHCII med dendritic cells regulate the reestablishment of vascular quiescence and stabilization after lymph node vascular expansion and suggest that these dendritic cells function in part to orchestrate the microenvironmental alterations required for successful immunity. |
