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

Abstract

Lymphocytes exit lymph nodes and return to the bloodstream through the efferent lymphatics. Cyster and colleagues show that lymphocytes exit into cortical sinuses by a pathway dependent on sphingosine 1-phosphate receptor type 1. The cellular dynamics of the egress of lymphocytes 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, whereas others returned to the parenchyma. T cells deficient in sphingosine 1-phosphate receptor type 1 probed the sinus surface but failed to enter the sinuses. In some sinuses, T cells became rounded and moved unidirectionally. 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 in which cortical sinus probing is followed by entry dependent on sphingosine 1-phosphate receptor type 1, capture of cells in a sinus region with flow, and transport to medullary sinuses and the efferent lymph.