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.

Quantification of lymph node transit times reveals differences in antigen surveillance strategies of naïve CD4 + and CD8 + T cells

“…This model is consistent with the wide distribution of residence times of a given T-cell population entering the LN at the same time (28). It is also consistent with microscopy data demonstrating the random walk behavior of individual T cells along fibroblastic reticular cells within LNs (3,4) and the probabilistic nature of their egress at lymphatic sinuses (29), both of which would be difficult to reconcile with a fixed LN dwell time.…”

Expansion of Cortical and Medullary Sinuses Restrains Lymph Node Hypertrophy during Prolonged Inflammation

“…Most research on lymphocyte egress from DLNs has been carried out in homeostatic conditions and focused either on mechanisms that lymphocytes use to reach efferent lymphatic vessels, including regulation of CCR7 (7) and sphingosine 1-phosphate receptor-1 (S1P1) expression (18,29,30,53,54), or on mechanisms operating at the level of lymphatic endothelial barriers (31,55). We showed that the expansion of cortical and medullary sinuses in the late phase of inflammation functionally supports the egress of naive lymphocytes from LNs.…”

“…We hypothesized that the return of lymphocyte egress to baseline levels at day 14 postimmunization compared with day 4 may occur through an expansion of cortical and medullary sinuses, because they are the major exit paths for lymphocytes (29)(30)(31). To investigate this possible scenario, we developed a strategy to distinguish cortical and medullary sinuses from subcapsular sinuses given that specific markers to differentiate them are currently lacking.…”

Differential requirement for ROCK in dendritic cell migration within lymphatic capillaries in steady-state and inflammation

“…35,36 Therefore, to date, LVs have mainly been visualized in IVM by in vivo labeling with intracutaneously injected fluorescent antibodies. 4,37,38 However, antibody labeling is considered less optimal for IVM than endogenous expression of fluorophores; it is typically restricted to the injection site and downstream regions and could interfere with leukocyte-endothelium interactions or lead to unwanted immune activation. To bypass these potential problems, we bred mice expressing Cre-recombinase 24 with RFP reporter mice.…”