Cortical sinus probing, S1P1-dependent entry and flow-based capture of egressing T cells

Abstract

The cellular dynamics of lymphocyte egress from lymph nodes are poorly defined. Here, we visualized the branched organization of lymph node cortical sinuses and found that after entry some T cells were retained while others returned to the parenchyma. Sphingosine-1-phosphate receptor 1 (S1P1)-deficient T cells probed the sinus surface but failed to enter. In some sinuses T cells became rounded and moved in a unidirectional fashion. T cells traveled from cortical sinuses into macrophage-rich sinus areas. Many T cells flowed from medullary sinuses into the subcapsular space. We propose a multistep model of lymph node egress where cortical sinus probing is followed by S1P1-dependent entry, capture of cells in a sinus region with flow and transport to medullary sinuses and the efferent lymph.