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

Recent studies have identified cortical sinuses as sites of sphingosine-1-phosphate receptor-1 (S1P₁)-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...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2010-11, Vol.107 (47), p.20447-20452
Main Authors: Grigorova, Irina L., Panteleev, Mikhail, Cyster, Jason G., Cooper, Max D.
Format: Article
Language:English
Subjects:
Animals
Antibodies
Antigens
Antigens, CD - genetics
Antigens, CD - immunology
Antigens, Differentiation, T-Lymphocyte - genetics
Antigens, Differentiation, T-Lymphocyte - immunology
B lymphocytes
Biological Sciences
CD69 antigen
Cell Movement - immunology
Cortex
Data processing
Flow Cytometry
Follicles
Inflammation
Lectins, C-Type - genetics
Lectins, C-Type - immunology
Leukocyte migration
Lymph
Lymph nodes
Lymph Nodes - anatomy & histology
Lymph Nodes - immunology
Lymph Nodes - secretion
Lymphocytes
Lymphocytes - immunology
Lymphocytes - secretion
Lymphocytes B
Lymphocytes T
Mathematical models
Mice
Mice, Inbred C57BL
Mice, Knockout
Microscopy
Microscopy, Confocal
Models, Immunological
Parenchyma
Phosphates
Receptors, CXCR5 - genetics
Receptors, Lysosphingolipid - immunology
Sinus
Sinuses
Sphingosine 1-phosphate
T lymphocytes
Up regulation
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Summary:Recent studies have identified cortical sinuses as sites of sphingosine-1-phosphate receptor-1 (S1P₁)-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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1009968107