Lymphocytes: Recirculation

Abstract

Successful immunosurveillance requires endless patrolling of lymphoid tissues by lymphocytes in search of foreign antigens. Lymphocytes enter the lymphoid tissues either through the blood vessel walls or via the afferent lymphatic vessels. To leave the circulation, bloodborne lymphocytes first tether to the endothelial lining of the vessels and start to roll. After an activation step they firmly adhere and transmigrate through the vessel wall. They then navigate through the tissue stroma following chemotactic and other guidance molecules, possibly encounter their cognate antigens and eventually return via the lymphatic vessels back into the blood to be dispersed to the other tissues of the body. In this tightly controlled process called lymphocyte recirculation, different adhesion molecules and activation signals on the two opposing cell types play a critical role. Dysregulated lymphocyte recirculation is involved in the pathogenesis of many inflammatory diseases and immunodeficiencies, and nowadays several drugs target this process.

Key Concepts:

  • Lymphocytes continuously recirculate between blood and lymphoid organs.

  • Majority of the lymphocytes enter the lymph nodes via specialised vessels called high endothelial venules (HEV).

  • The remaining lymphocytes (15–20%), together with dendritic cells and antigens, enter the lymph nodes via afferent lymphatics.

  • Lymphocytes leave the lymph nodes via efferent lymphatics.

  • Lymphocyte recirculation allows the lymphocytes to meet their cognate antigens and other leucocyte subsets to evoke an efficient immune response.

  • Lymphocytes interact with the vessel wall in a multistep fashion, using several leucocyte surface molecules, which recognise their counter receptors on endothelial cells.

  • The rolling and tethering of lymphocytes on the vessel wall is mediated by selectins.

  • Chemokines and their receptors are needed to activate leucocyte integrins.

  • Activated integrins mediate firm adhesion between lymphocytes and endothelium.

  • The transmigration of leucocytes into the tissues requires adhesion molecules, proteinases and repair mechanisms.

Keywords: adhesion molecules; endothelium; extravasation; homing; transmigration; lymphatics

Figure 1.

Multistep cascade of lymphocyte extravasation. The bloodborne cell makes initially transient contacts with endothelial cells, which then result in rolling along the vascular lining. If the cell becomes activated, it can subsequently firmly adhere to the endothelial cells, seek for interendothelial junctions (crawling) and migrate through the endothelial monolayer (via para‐ or transcellular routes) and basement membrane into the tissue. The contribution of major super families of adhesion and activation molecules at each step is depicted below. E, endothelial layer; Bm, basement membrane.

Figure 2.

Molecules mediating lymphocyte recirculation. The most relevant proteins involved in lymphocyte–endothelial cell interactions are shown as receptor–ligand pairs.

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How to Cite close
Jalkanen, Sirpa, and Salmi, Marko(Feb 2013) Lymphocytes: Recirculation. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001200.pub3]