Disappearance and reappearance of high endothelial venules and immigrating lymphocytes in lymph nodes deprived of afferent lymphatic vessels: a possible regulatory role of macrophages in lymphocyte migration

Abstract

Interruption of the afferent lymphatic vessels of the popliteal lymph node resulted in the disappearance of high endothelial venules (HEV) and immigrating lymphocytes within 3 weeks. HEV showed several characteristic morphological changes: the endothelial cells became flattened and less pyroninophilic, the chromatine became condensed and protein synthetizing and secretory cell organelles became scarce. At the same time the number of macrophages in the lymph node was severely reduced. Injection of sheep red blood cells into such lymph nodes, 6 weeks after operation, resulted in reappearance of HEV and immigrating lymphocytes, and development of many plasma cells and some germinal centres. Injection of lipopolysaccharide into the operated lymph nodes resulted in the appearance of many plasma cells and a few poorly developed germinal centres; HEV and immigrating lymphocytes, however, remained almost absent. The results show a relationship between the immigration of lymphocytes and the activity of the endothelial cells in the HEV. The activation of the latter may occur by mediators released by antigen-stimulated macrophages and T cells. Moreover, the morphological features of the HEV are independent of the presence of recirculating lymphocytes.

Modulation of L-selectin ligand expression during an immune response accompanying tumorigenesis in transgenic mice.

“…The low frequency of L-selectin ligand-and MAd-CAM-1-expressing vessels suggests the possibility that other adhesion molecules could mediate later stages of the inflammation. Soluble factors released by activated macrophages or lymphocytes have been implicated in regulation of PNAd and MAdCAM-1 expression on HEV in lymph nodes (56)(57)(58) and may also be involved in islets. Similarly, VCAM-1 expression on endothelial cells is induced by several inflammatory signals (for review see reference 38).…”

Regulation of murine lymphokine production in vivo. III. The lymphoid tissue microenvironment exerts regulatory influences over T helper cell function.

“…Finally, our model possesses an additional important component . We hypothesize that the macrophage, already known to enter lymphoid organs predominantly through the afferent lymphatic drainage from the tissue sites (40), may play an extremely important immunologic role beyond antigen uptake, processing, and presentation . It is quite possible that the macrophage, as a consequence of inductive influences provided during its surveillance of peripheral or mucosal tissue sites, actually instructs the antigen-responsive T cell to produce specific species of lymphokines after its entrance into the draining lymphoid organ and its interaction with an antigen-responsive T cell .…”

Plasticity of endothelial cells: rapid dedifferentiation of freshly isolated high endothelial venule endothelial cells outside the lymphoid tissue microenvironment

“…Previous studies in rodents on the influence of afferent lymphatic vessel interruption in peripheral lymph nodes have revealed that lymph constituents are required to maintain the specialized features of the HEVEC phenotype, including plump EC morphology, expression of MECA-79-positive sulfated L-selectin ligands, and ability to support L-selectinmediated binding and lymphocyte traffic in vivo. 30,31 The HEVspecific fucosyltransferase Fuc-TVII was decreased after 5 days and completely lost after 8 days. 50 Our findings of rapid downregulation of Fuc-TVII mRNA levels in dedifferentiated human HEVECs (Figure 2) are in agreement with these later findings in mice.…”

“…29 A critical role of the microenvironment in HEV specialization has been suggested by studies in rodents; when peripheral lymph nodes were deprived of afferent lymph, the HEV converted to a flat-walled EC morphology without MECA-79 reactivity or the ability to support lymphocyte traffic. 30,31 In this study, we used a combination of reverse transcriptionpolymerase chain reaction (RT-PCR) and DNA microarray experiments to compare gene expression patterns between HEVECs freshly isolated from human tonsils without any cell culture step (D0 HEVECs) and dedifferentiated HEVECs cultured outside the lymphoid tissue microenvironment for 48 hours (D2 HEVECs). We found a rapid and striking down-regulation of several key HEV genes in the dedifferentiated HEVECs, including DARC 11 and fucosyltransferase Fuc-TVII.…”