Preface

Continuous lymphocyte migration to normal gut is a prerequisite for immune homoeostasis in humans. In this review we briefly describe the physiology of lymphocyte recirculation through the bowel. The adhesion molecules mediating the lymphocyte–endothelial interactions in the gut during the multistep extravasation cascade will be presented in the light of their ability to confer mucosal selectivity of lymphocyte trafficking. We will also discuss the relevance of leucocyte recirculation in respect to bowel inflammation and mucosal vaccination, and its potential in the anti-inflammatory treatment of gastrointestinal diseases.

Lymphocyte recirculation—the general theme

The gut is the main portal of antigen entry into the body and lymphocytes are responsible for mounting an adequate immune response against harmful antigens. As each lymphocyte only carries an antigen receptor for a single antigen, a huge number of lymphocytes, each specific for a different antigen, are produced in the bone marrow and thymus each day. These naive cells must then be able to sample freely all different tissues of the body in search of their cognate antigens. To maximise the likelyhood of the rare possibility that a given lymphocyte would find its cognate antigen introduced anywhere in the body, a sophisticated system of lymphocyte recirculation has evolved.1-4

In this process, lymphocytes continuously patrol between the blood and different tissues of the body. Initially blood borne lymphocytes leave the circulation via secondary lymphoid tissues like lymph nodes. The exit from the blood mainly takes place in distinct postcapillary vessels called high endothelial venules (HEV), which display several unique structural and functional modifications to facilitate extravasation.5 Foreign antigens are retrieved and concentrated from distal epithelial surfaces via the afferent lymphatic system into the secondary lymphoid organs.

When an extravasated lymphocyte finds its antigen in the supportive context of the secondary lymphoid tissues, it starts to proliferate and differentiate and gives rise …