Article

Lymph node cortical sinus organization and relationship to lymphocyte egress dynamics and antigen exposure

The Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California, San Francisco, CA 94143, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 11/2010; 107(47):20447-52. DOI: 10.1073/pnas.1009968107
Source: PubMed

ABSTRACT

Recent studies have identified cortical sinuses as sites of sphingosine-1-phosphate receptor-1 (S1P(1))-dependent T- and B-cell egress from the lymph node (LN) parenchyma. However, the distribution of cortical sinuses in the entire LN and the extent of lymph flow within them has been unclear. Using 3D reconstruction and intravital two-photon microscopy we describe the branched organization of the cortical sinus network within the inguinal LN and show that lymphocyte flow begins within blunt-ended sinuses. Many cortical sinuses are situated adjacent to high endothelial venules, and some lymphocytes access these sinuses within minutes of entering a LN. However, upon entry to inflamed LNs, lymphocytes rapidly up-regulate CD69 and are prevented from accessing cortical sinuses. Using the LN reconstruction data and knowledge of lymphocyte migration and cortical sinus entry dynamics, we developed a mathematical model of T-cell egress from LNs. The model suggests that random walk encounters with lymphatic sinuses are the major factor contributing to LN transit times. A slight discrepancy between predictions of the model and the measured transit times may be explained by lymphocytes undergoing a few rounds of migration between the parenchyma and sinuses before departing from the LN. Because large soluble antigens gain rapid access to cortical sinuses, such parenchyma-sinus shuttling may facilitate antibody responses.

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Available from: Irina L. Grigorova
    • "The fluid flow through the node has been linked to reducing the preference of cells to migrate within the node, causing more of the immune cells to exit the node (Grigorova et al. 2010). As the lymph nodes are involved in antigen sensing and immune cell activation, understanding how fluid is transported through the node could be useful for developing knowledge of how fluid movement affects the immune response of the node. "
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    • "Images were processed and analyzed using Volocity imaging software. Histocytometric analysis of reconstructions was performed with CellProfiler (Carpenter et al., 2006; Grigorova et al., 2010), and CellProfiler Analyst (Hickman et al., 2008; Jones et al., 2008; León et al., 2012). Analysis of reconstructions was performed with individual XY imaging planes, which were representative of at least 400 µm of reconstructed LNs. "
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