Intracellular signaling pathways mediating lymphocyte trafficking

Lymphocytes migrate from the blood stream into secondary lymphoid organs (SLO), where antigens (Ag) collected in the periphery are displayed on the surface of Ag-presenting cells. Continuous lymphocyte recirculation throughout SLO greatly increases the chances that rare Agspecific T and B cells encounter their cognate Ag, making it a prerequisite for effective immune surveillance. Members of the chemokine family of proteins, as well as the lipid mediator sphingosine-1-phosphate (S1P), are the main factors orchestrating dynamic trafficking of lymphocytes. They exert this control by activating specific receptors, which promote lymphocyte adhesion inside specific microvessels of SLO, subsequent migration inside lymphoid tissue and egress into the blood. This article covers our current understanding of the complex intracellular signaling mechanisms that are activated downstream of these receptors and contribute to lymphocyte recirculation.