Molecular determinants controlling homeostatic recirculation and tissue-specific trafficking of lymphocytes

The homeostasis of the immune system is maintained by the recirculation of naïve lymphocytes through the secondary lymphoid tissues, such as the lymph nodes, Peyer's patches, and spleen. Upon insult by pathogens or antigens, lymphocytes become activated, and the regulated trafficking of these cells results in the integration of systemic and regional immune responses. The exquisite specificity of such lymphocyte trafficking is determined by tissue-specific guidance signals expressed by the endothelial cells of postcapillary venules, combined with counterreceptors expressed by the circulating lymphocytes. The high endothelial venules can selectively guide naïve lymphocytes into the lymph nodes and Peyer's patches by expressing a unique combination of vascular addressins, lymphocyte-specific chemokines, and chemokine-binding molecules. The inflamed postcapillary venules in extralymphoid tissues, such as the skin and intestinal lamina propria, also use a distinct array of endothelial adhesion molecules and tissue- selective chemokines, and support the recruitment of effector and memory lymphocytes that express the appropriate receptors for tissue-specific trafficking. In this review, we summarize the present understanding of the homeostatic recirculation of naïve lymphocytes through the secondary lymphoid tissues and the specific targeting of antigen-experienced lymphocytes into the effector sites. We also revisit some previous studies that reported apparently conflicting observations.