scholarly journals Entry of naive CD4 T cells into peripheral lymph nodes requires L-selectin.

1994 ◽  
Vol 180 (6) ◽  
pp. 2401-2406 ◽  
Author(s):  
L M Bradley ◽  
S R Watson ◽  
S L Swain
Keyword(s):  
Lymph Node ◽  
Lymph Nodes ◽  
Systemic Exposure ◽  
Keyhole Limpet Hemocyanin ◽  
Cd4 Cells ◽  
High Endothelial Venules ◽  
T Cell Migration ◽  
Peripheral Lymph ◽  
Cd4 Cell

Binding of L-selectin expressed on lymphocytes to carbohydrate ligand(s) on lymph node high endothelial venules is thought to initiate lymphocyte extravasation from blood to lymph during recirculation and localization to sites of antigen (Ag) exposure. Previous studies have shown that treatment of lymphocytes with antibody to L-selectin (MEL-14) ablates trafficking to peripheral lymph nodes (PLN). In mice, naive but not memory CD4 cells express L-selectin. To examine the role of L-selectin in helper T cell migration, we studied the effects of in vivo administration of MEL-14 on CD4 cell responses. Systemic exposure of mice to MEL-14 depleted CD4 cells expressing a naive phenotype (CD45RBhi, CD44lo) from PLN but not from spleen. The majority of residual lymph node CD4 cells exhibited the reciprocal, memory phenotype (CD45RBlo, CD44hi). MEL-14 treatment prevented priming of naive CD4 cells for proliferation and cytokine production (IL-2 and IL-4) to keyhole limpet hemocyanin in PLN draining the site of Ag injection, but not in the spleen. The results suggest that naive cells were not depleted, but rather diverted to other sites where priming occurred. The data demonstrate that L-selectin mediates extravasation of naive CD4 cells into PLN and that its function cannot be replaced by other homing receptors.

scholarly journals The influence of afferent lymphatic vessel interruption on vascular addressin expression.

1991 ◽  
Vol 115 (1) ◽  
pp. 85-95 ◽  
Author(s):  
R E Mebius ◽  
P R Streeter ◽  
J Brevé ◽  
A M Duijvestijn ◽  
G Kraal
Keyword(s):  
Lymph Node ◽  
Lymph Nodes ◽  
Lymphatic Vessel ◽  
Lymphatic Vessels ◽  
Lymphoid Tissues ◽  
Peripheral Lymph Node ◽  
Lymphocyte Homing ◽  
High Endothelial Venules ◽  
Peripheral Lymph

Tissue-selective lymphocyte homing is directed in part by specialized vessels that define sites of lymphocyte exit from the blood. These vessels, the post capillary high endothelial venules (HEV), are found in organized lymphoid tissues, and at sites of chronic inflammation. Lymphocytes bearing specific receptors, called homing receptors, recognize and adhere to their putative ligands on high endothelial cells, the vascular addressins. After adhesion, lymphocytes enter organized lymphoid tissues by migrating through the endothelial cell wall. Cells and/or soluble factors arriving in lymph nodes by way of the afferent lymph supply have been implicated in the maintenance of HEV morphology and efficient lymphocyte homing. In the study reported here, we assessed the influence of afferent lymphatic vessel interruption on lymph node composition, organization of cellular elements; and on expression of vascular addressins. At 1 wk after occlusion of afferent lymphatic vessels, HEV became flat walled and expression of the peripheral lymph node addressin disappeared from the luminal aspect of most vessels, while being retained on the abluminal side. In addition, an HEV-specific differentiation marker, defined by mAb MECA-325, was undetectable at 7-d postocclusion. In vivo homing studies revealed that these modified vessels support minimal lymphocyte traffic from the blood. After occlusion, we observed dramatic changes in lymphocyte populations and at 7-d postsurgery, lymph nodes were populated predominantly by cells lacking the peripheral lymph node homing receptor LECAM-1. In addition, effects on nonlymphoid cells were observed: subcapsular sinus macrophages, defined by mAb MOMA-1, disappeared; and interdigitating dendritic cells, defined by mAb NLDC-145, were dramatically reduced. These data reveal that functioning afferent lymphatics are centrally involved in maintaining normal lymph node homeostasis.

CD44-dependent lymphoma cell dissemination: a cell surface CD44 variant, rather than standard CD44, supports in vitro lymphoma cell rolling on hyaluronic acid substrate and its in vivo accumulation in the peripheral lymph nodes

2001 ◽  
Vol 114 (19) ◽  
pp. 3463-3477
Author(s):  
Shulamit B. Wallach-Dayan ◽  
Valentin Grabovsky ◽  
Jürgen Moll ◽  
Jonathan Sleeman ◽  
Peter Herrlich ◽  
...  
Keyword(s):  
Cell Migration ◽  
Hyaluronic Acid ◽  
Lymph Node ◽  
Cell Surface ◽  
Lymph Nodes ◽  
Local Tumor ◽  
Cd44 Variant ◽  
Peripheral Lymph

Cell motility is an essential element of tumor dissemination, allowing organ infiltration by cancer cells. Using mouse LB lymphoma cells transfected with standard CD44 (CD44s) cDNA (LB-TRs cells) or with the alternatively spliced CD44 variant CD44v4-v10 (CD44v) cDNA (LB-TRv cells), we explored their CD44-dependent cell migration. LB-TRv cells, but not LB-TRs or parental LB cells, bound soluble hyaluronic acid (HA) and other glycosaminoglycans (GAGs), and exclusively formed, under physiological shear force, rolling attachments on HA substrate. Furthermore, LB-TRv cells, but not LB-TRs cells or their parental LB cells, displayed accelerated local tumor formation and enhanced accumulation in the peripheral lymph nodes after s.c. inoculation. The aggressive metastatic behavior of i.v.-injected LB-TRV cells, when compared with that of other LB-transfectants, is attributed to more efficient migration to the lymph nodes, rather than to local growth in the lymph node. Injection of anti-CD44 monoclonal antibody or of the enzyme hyaluronidase also prevented tumor growth in lymph nodes of BALB/c mice inoculated with LB-TRv cells. The enhanced in vitro rolling and enhanced in vivo local tumor growth and lymph node invasion disappeared in LB cells transfected with CD44v cDNA bearing a point mutation at the HA binding site, located at the distal end of the molecule constant region. These findings show that the interaction of cell surface CD44v with HA promotes cell migration both in vitro and in vivo, and they contribute to our understanding of the mechanism of cell trafficking, including tumor spread.

scholarly journals Adhesive mechanisms governing interferon-producing cell recruitment into lymph nodes

2005 ◽  
Vol 202 (5) ◽  
pp. 687-696 ◽  
Author(s):  
Thomas G. Diacovo ◽  
Amanda L. Blasius ◽  
Tak W. Mak ◽  
Marina Cella ◽  
Marco Colonna
Keyword(s):  
Lymph Nodes ◽  
Nk Cell ◽  
High Endothelial Venules ◽  
Cell Recruitment ◽  
Cell Responses ◽  
Peripheral Lymph ◽  
Chemokine Receptor Ccr5 ◽  
Gain Access ◽  
Receptor Ccr5

Natural interferon-producing cells (IPCs) are found in peripheral lymph nodes (PLNs), where they support NK cell, T cell, and B cell responses to pathogens. However, their route of entry and the adhesive mechanisms used to gain access to PLNs remain poorly defined. We report that IPCs can enter PLNs via a hematogenous route, which involves a multistep adhesive process, and that transmigration is enhanced by inflammation. Results indicate that L-selectin on IPCs is required for efficient attachment and rolling on high endothelial venules in vivo in both nonstimulated and inflamed PLNs. IPCs, however, also possess functional ligands for E-selectin that contribute to this process only in the latter case. In conjunction with selectin-mediated adhesion, both β1- and β2-integrins participate in IPC attachment to the inflamed vessel wall, whereas chemotaxis relies in part on the chemokine receptor CCR5. Identification of the adhesive machinery required for IPC trafficking into PLNs may provide opportunities to regulate immune responses reliant on the activity of these cells.

scholarly journals Immunohistologic and functional characterization of a vascular addressin involved in lymphocyte homing into peripheral lymph nodes.

1988 ◽  
Vol 107 (5) ◽  
pp. 1853-1862 ◽  
Author(s):  
P R Streeter ◽  
B T Rouse ◽  
E C Butcher
Keyword(s):  
Endothelial Cells ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Peyer's Patches ◽  
Peripheral Lymph Node ◽  
Lymphocyte Homing ◽  
Tissue Specific ◽  
Peripheral Lymph

The tissue localization or "homing" of circulating lymphocytes is directed in part by specialized vessels that define sites of lymphocyte exit from the blood. In peripheral lymph nodes, mucosal lymphoid tissues (Peyer's patches and appendix), and sites of chronic inflammation, for example, lymphocytes leave the blood by adhering to and migrating between those endothelial cells lining postcapillary high endothelial venules (HEV). Functional analyses of lymphocyte interactions with HEV have shown the lymphocytes can discriminate between HEV in different tissues, indicating that HEV express tissue-specific determinants or address signals for lymphocyte recognition. We recently described such a tissue-specific "vascular addressin" that is selectively expressed by endothelial cells supporting lymphocyte extravasation into mucosal tissues and that appears to be required for mucosa-specific lymphocyte homing (Streeter, P. R., E. L. Berg, B. N. Rouse, R. F. Bargatze, and E. C. Butcher. 1988. Nature (Lond.). 331:41-46). Here we document the existence and tissue-specific distribution of a distinct HEV differentiation antigen. Defined by monoclonal antibody MECA-79, this antigen is expressed at high levels on the lumenal surface and in the cytoplasm of HEV in peripheral lymph nodes. By contrast, although MECA-79 stains many HEV in the mucosal Peyer's patches, expression in most cases is restricted to the perivascular or ablumenal aspect of these venules. In the small intestine lamina propria, a mucosa-associated site that supports the extravasation of lymphocytes, venules do not stain with MECA-79. Finally, we demonstrate that MECA-79 blocks binding of both normal lymphocytes and a peripheral lymph node-specific lymphoma to peripheral lymph node HEV in vitro and that it also inhibits normal lymphocyte homing to peripheral lymph nodes in vivo without significantly influencing lymphocyte interactions with Peyer's patch HEV in vitro or in vivo. Thus, MECA-79 defines a novel vascular addressin involved in directing lymphocyte homing to peripheral lymph nodes.

Rap1 controls lymphocyte adhesion cascade and interstitial migration within lymph nodes in RAPL-dependent and -independent manners

Blood ◽  
2010 ◽  
Vol 115 (4) ◽  
pp. 804-814 ◽  
Author(s):  
Yukihiko Ebisuno ◽  
Koko Katagiri ◽  
Tomoya Katakai ◽  
Yoshihiro Ueda ◽  
Tomomi Nemoto ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Critical Role ◽  
Small Gtpase ◽  
High Endothelial Venules ◽  
Lymphocyte Adhesion ◽  
Peripheral Lymph ◽  
Directional Movement ◽  
Lymphocyte Motility

Abstract The small GTPase Rap1 and its effector RAPL regulate lymphocyte adhesion and motility. However, their precise regulatory roles in the adhesion cascade preceding entry into lymph nodes and during interstitial migration are unclear. Here, we show that Rap1 is indispensably required for the chemokine-triggered initial arrest step of rolling lymphocytes through LFA-1, whereas RAPL is not involved in rapid arrest. RAPL and talin play a critical role in stabilizing lymphocyte arrest to the endothelium of blood vessels under flow or to the high endothelial venules of peripheral lymph nodes in vivo. Further, mutagenesis and peptide studies suggest that release of a trans-acting restraint from the β2 cytoplasmic region of LFA-1 is critical for Rap1-dependent initial arrest. Rap1 or RAPL deficiency severely impaired lymphocyte motility over lymph node stromal cells in vitro, and RAPL deficiency impaired high-velocity directional movement within lymph nodes. These findings reveal the several critical steps of Rap1, which are RAPL-dependent and -independent, in lymphocyte trafficking.

scholarly journals L-selectin controls trafficking of chronic lymphocytic leukemia cells in lymph node high endothelial venules in vivo

Blood ◽  
2015 ◽  
Vol 126 (11) ◽  
pp. 1336-1345 ◽  
Author(s):  
Fanny Lafouresse ◽  
Elisabeth Bellard ◽  
Camille Laurent ◽  
Christine Moussion ◽  
Jean-Jacques Fournié ◽  
...  
Keyword(s):  
Lymph Node ◽  
Chronic Lymphocytic Leukemia ◽  
Lymph Nodes ◽  
In Vivo Imaging ◽  
Lymphocytic Leukemia ◽  
Leukemia Cells ◽  
High Endothelial Venules ◽  
Key Points

Key Points In vivo imaging reveals that CLL cells bind to lymph node high endothelial venules via an L-selectin–dependent multistep adhesion cascade. Interference with L-selectin–mediated trafficking in high endothelial venules could limit dissemination of CLL cells to lymph nodes.

Salmonella Persistence within the Peripheral Lymph Nodes of Cattle following Experimental Inoculation

2016 ◽  
Vol 79 (6) ◽  
pp. 1032-1035 ◽  
Author(s):  
T. S. EDRINGTON ◽  
G. H. LONERAGAN ◽  
K. J. GENOVESE ◽  
D. L. HANSON ◽  
D. J. NISBET
Keyword(s):  
Body Weight ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Enrichment Culture ◽  
Lower Leg ◽  
Challenge Strain ◽  
Peripheral Lymph ◽  
Experimental Inoculation ◽  
Duration Of Infection

ABSTRACT Utilizing a transdermal method of inoculation developed in our laboratory, the duration of infection of Salmonella in the peripheral lymph nodes of steers was examined. Thirty-six Holstein steers (mean body weight of 137 kg) were inoculated with Salmonella Montevideo (day 0) on each lower leg and both sides of the back and abdomen. Calves were euthanized beginning at 6 h and subsequently on each of days 1, 2, 4, 7, 9, 11, 14, and 21 postinoculation (four animals each time). The subiliac, popliteal, and superficial cervical (prescapular) lymph nodes were collected and cultured (quantitatively and qualitatively) for the challenge strain of Salmonella. The challenge strain was detected via direct culture within the lymph nodes at 6 h postinoculation and on each subsequent necropsy date. Salmonella levels in lymph node were 0.8 to 1.8 log CFU/g. Lymph nodes were generally positive after enrichment culture throughout the experiment. Salmonella elimination appeared to begin approximately 14 days postinoculation. However, elimination was not completed by day 21; therefore, a second experiment was conducted identical to the first except that the time from inoculation to necropsy was extended. Salmonella was recovered via direct culture on each of the necropsy days, and results in general were similar to those of experiment I, except that on days 20, 24, and 28 isolates from serogroups C2 and E1 were identified in addition to the inoculation strain C1 in multiple animals. The data from both experiments indicate that after a single inoculation event, Salmonella would be completely cleared by approximately 28 days. Further research with expanded times between inoculation and necropsy is required for verification.

SS9-6 In vivo imaging of high endothelial venules and lymphatic vessels in lymph nodes and tertiary lymphoid organs

Cytokine ◽  
2010 ◽  
Vol 52 (1-2) ◽  
pp. 77
Author(s):  
Nancy H. Ruddle ◽  
Lucy A. Truman ◽  
Kevin L. Bentley.
Keyword(s):  
Lymph Nodes ◽  
In Vivo Imaging ◽  
Lymphatic Vessels ◽  
Lymphoid Organs ◽  
High Endothelial Venules

scholarly journals Demonstration that a lectin-like receptor (gp90MEL) directly mediates adhesion of lymphocytes to high endothelial venules of lymph nodes.

1989 ◽  
Vol 109 (5) ◽  
pp. 2463-2469 ◽  
Author(s):  
J S Geoffroy ◽  
S D Rosen
Keyword(s):  
Lymph Node ◽  
Lymphoid Organ ◽  
Lymphoid Organs ◽  
Surface Glycoprotein ◽  
Lymphocyte Migration ◽  
Peripheral Lymph Node ◽  
Adhesive Interaction ◽  
High Endothelial Venules ◽  
Cell Surface Glycoprotein ◽  
Peripheral Lymph

Lymphocyte migration from the blood into most secondary lymphoid organs is initiated by a highly selective adhesive interaction with the endothelium of specialized blood vessels known as high endothelial venules (HEV). The propensity of lymphocytes to migrate to particular lymphoid organs is known as lymphocyte homing, and the receptors on lymphocytes that dictate interactions with HEV at particular anatomical sites are designated "homing receptors". Based upon antibody blockade experiments and cell-type distribution studies, a prominent candidate for the peripheral lymph node homing receptor in mouse is the approximately 90-kD cell surface glycoprotein (gp90MEL) recognized by the monoclonal antibody MEL-14. Previous work, including sequencing of a cDNA encoding for this molecule, supports the possibility that gp90MEL is a calcium-dependent lectin-like receptor. Here, we show that immunoaffinity-purified gp90MEL interacts in a sugar-inhibitable manner with sites on peripheral lymph node HEV and prevents attachment of lymphocytes. Lymphocyte attachment to HEV in Peyer's patches, a gut-associated lymphoid organ, is not affected by gp90MEL. The results demonstrate that gp90MEL, as a lectin-like receptor, directly bridges lymphocytes to the endothelium.

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