High endothelial venules

Source: Wikipedia, the free encyclopedia.

High endothelial venules (HEV) are specialized post-

lymphocytes circulating in the blood to directly enter a lymph node (by crossing through the HEV).[2][3]

In humans, HEVs are found in all

leukocytes (express specialized ligands for lymphocytes and are able to support high levels of lymphocyte extravasation).[4] HEVs enable naïve lymphocytes to move in and out of the lymph nodes from the circulatory system. HEV cells express addressins, which are specific adhesion molecules that attach to the L-selectins
on lymphocytes and anchor them to the HEV wall in preparation for crossing the endothelium.

The endothelial cells of HEVs have a 'plump' appearance different from the flat morphology of endothelial cells that line other vessels, and are therefore called high endothelial cells by reference to their thickness.[4] Another characteristic of HEVs, revealed by light-microscopic examination, is the presence of a large number of lymphocytes within their walls. This illustrates the function of HEVs in lymphocyte recruitment and explains why these vessels were implicated in lymphocyte traffic from the time of their initial description.

The need for HEV

In order to have an

dendritic cells.[5]
In order for naïve T cells to bind to their specific antigen, they need to experience physical contact with those cells. Since antigen levels are usually low, contact in blood circulation would be unlikely. Therefore, T cells need a region where they can go to sample foreign antigens that have entered the body. When an APC, such as a dendritic cell, binds a foreign antigen; it becomes activated and moves into the lymph nodes (sites for antigen sampling by T cells) via afferent lymphatic vessels. Naïve T cells in the circulation regularly move through the lymph nodes via HEV in order to scan the APC for foreign antigens. When they encounter such an antigen, the cell becomes activated, resulting in the immune system mounting a response against the causative agent of the infection.

Depletion of

CD11c+ dendritic cells in mouse significantly altered the phenotype of HEV. The normal phenotype of HEV is possibly maintained by DC-secreted lymphotoxin (TNF-beta).[6]

Cell movement through HEV

HEV cuboidal endothelial cells express the adhesion molecules GlyCAM-1 (in mucosal HEV this is MAdCAM-1), ICAM-1 and CD34. They also secrete the chemokine CCL21. Naïve T cells express CCR7 receptor and adhesion molecules L-selectin and LFA-1.[5] As naïve T cells move through the circulation, they 'roll' over the endothelial cells in the vessel walls. The rolling mechanism helps the L-selectin molecules on the surface of naive T cells to weakly interact with GlyCAM-1 and CD34 molecules on HEV cells. The chemokine CCL21 then binds to its receptor CCR7 expressed on the T cell. This binding induces a conformational change in the LFA-1 molecule causing it to bind tightly to ICAM-1.[7] This tight binding stops further movement of the T cell which can then move between HEV cells into the lymph node by a process termed 'diapedesis' (or extravasation).

Markers

Despite intensive efforts, few HEV-specific markers have been described. The best HEV marker currently available is a carbohydrate epitope recognized by the monoclonal antibody (mAb) MECA-79, which stains all HEVs within lymphoid tissues and does not react with postcapillary venules or large vessels in spleen, thymus or nonlymphoid tissues. MECA-79 mAb inhibits lymphocyte emigration through HEVs into lymph nodes in vivo and lymphocyte adhesion to lymph node and tonsil HEVs in vitro. Although initially produced against mouse HEVs, the mAb shows a wide crossreactivity among species. The MECA-79 carbohydrate epitope decorates a family of HEV counter-receptors for L-selectin, both in mouse and human16. Another mAb, HECA-452, recognizing a carbohydrate epitope expressed on human HEVs but not on other vessels, has been described. Nevertheless, unlike MECA-79, this mAb is not HEV specific: HECA-452 recognizes a carbohydrate epitope related to the

sialyl-Lewis a oligosaccharides and, in addition to reacting with high endothelium, crossreacts with monocytic cells, dendritic cells and a subset of skin-homing memory lymphocytes.[4]

Furthermore, two other HEV markers have been described in the mouse:

  1. the mAb MECA-325 defines an antigen that can be induced in nonlymphoid endothelial cells by interferon γ ( IFN- γ); and
  2. the mAb MECA-367 recognizes mucosal addressin cell adhesion molecule 1 (MAdCAM-1), a counter-receptor for L-selectin and α4β7 integrin that is expressed in mucosal HEVs and in venules of intestinal lamina propria but can be induced in nonmucosal endothelial cells by tumor necrosis factor cx (TNF- α) and IL-l.[4]

In chronic human inflammatory disease

The vessels with HEV characteristics appear in human tissue in association with long-standing chronic inflammation.

autoimmune thyroiditis (Graves' disease and Hashimoto's thyroiditis), areas of dense lymphocytic infiltration contain vessels with plump endothelium expressing MECA-79 and HECA-452. These observations suggest that HEVs could play an important role in the pathogenesis of these diseases by mediating abnormal lymphocyte recruitment to the gut or the thyroid. MECA-79+ venules with plump endothelium have also been detected in other sites of chronic inflammation, including many cutaneous inflammatory lesions. The presence of MECA-79+ HEV-like vessels in many different human chronic inflammatory diseases indicates that L-selectin is likely to play a major role in lymphocyte emigration at chronic inflammatory sites.[4]

References

  1. PMC 8487881
    .
  2. ISBN 978-1-4292-0211-4
    . Table 14-1
  3. ISBN 978-1-4160-2999-1
    .
  4. ^
    PMID 7546210
    .
  5. ^
    ISBN 0-8153-4101-6
    .
  6. doi:10.1038/nature10540
  7. ISBN 978-0-19-920614-8
    .
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