The Experts below are selected from a list of 243 Experts worldwide ranked by ideXlab platform
Jeanphilippe Girard - One of the best experts on this subject based on the ideXlab platform.
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dendritic cells control Lymphocyte entry to lymph nodes through high endothelial venules
Nature, 2011Co-Authors: Christine Moussion, Jeanphilippe GirardAbstract:Christine Moussion and Jean-Philippe Girard report that dendritic cells in the immune system have an unexpected immune surveillance role in Lymphocyte recirculation during homeostasis. Lymphotoxin ligands derived from dendritic cells promote the growth of high endothelial venules — blood vessels specialized in Lymphocyte recruitment — which control the entry of naive Lymphocytes from the blood into lymph nodes. While patrolling the body in search of foreign antigens, naive Lymphocytes continuously circulate from the blood, through the lymph nodes, into the lymphatic vessels and back to the blood1,2. This process, called Lymphocyte recirculation, provides the body with effective immune surveillance for foreign invaders and for alterations to the body’s own cells. However, the mechanisms that regulate Lymphocyte recirculation during homeostasis remain incompletely characterized. Here we show that dendritic cells (DCs), which are well known for their role in antigen presentation to T Lymphocytes3, control the entry of naive Lymphocytes to lymph nodes by modulating the phenotype of high endothelial venules (HEVs), which are blood vessels specialized in Lymphocyte recruitment2,4,5. We found that in vivo depletion of CD11c+ DCs in adult mice over a 1-week period induces a reduction in the size and cellularity of the peripheral and mucosal lymph nodes. In the absence of DCs, the mature adult HEV phenotype reverts to an immature neonatal phenotype, and HEV-mediated Lymphocyte recruitment to lymph nodes is inhibited. Co-culture experiments showed that the effect of DCs on HEV endothelial cells is direct and requires lymphotoxin-β-receptor-dependent signalling. DCs express lymphotoxin, and DC-derived lymphotoxin is important for Lymphocyte homing to lymph nodes in vivo. Together, our results reveal a previously unsuspected role for DCs in the regulation of Lymphocyte recirculation during immune surveillance.
Joan M Cookmills - One of the best experts on this subject based on the ideXlab platform.
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vascular cell adhesion molecule 1 vcam 1 activation of endothelial cell matrix metalloproteinases role of reactive oxygen species
Blood, 2004Co-Authors: Tracy L Deem, Joan M CookmillsAbstract:Lymphocytes bound at endothelial cell junctions extravasate within minutes. Lymphocyte-endothelial cell binding is mediated by receptors such as vascular cell adhesion molecule 1 (VCAM-1). VCAM-1 activates endothelial cell nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in minutes, and this activity is required for VCAM-1–dependent Lymphocyte migration. In this report, we examined mechanisms for activation of matrix metalloproteinases (MMPs) during VCAM-1–dependent Lymphocyte migration. Lymphocyte binding to VCAM-1 rapidly activated endothelial cell-associated MMPs. Furthermore, inhibition of MMPs on the endothelial cells but not on the Lymphocytes blocked VCAM-1–dependent Lymphocyte migration across endothelial cells. The activation of endothelial cell MMPs required VCAM-1–stimulated endothelial cell NADPH oxidase activity as determined by scavenging of reactive oxygen species (ROS) and by pharmacologic or antisense inhibition of NADPH oxidase. Exogenous addition of 1 μM H2O2, the level of H2O2 generated by VCAM-1–stimulated endothelial cells, rapidly activated endothelial cell-associated MMPs. In contrast, activation of Lymphocyte-associated MMPs was delayed by hours after binding to VCAM-1, and this activation was blocked by inhibition of endothelial cell ROS generation. There was also a delay in H2O2-induced decrease in Lymphocyte-associated tissue inhibitors of metalloproteinases (TIMPs), resulting in an increase in MMP/TIMP ratio. In summary, this is the first report of a mechanism for ROS function in VCAM-1 activation of endothelial cell MMPs during VCAM-1–dependent Lymphocyte migration.
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human and murine high endothelial venule cells phagocytose apoptotic leukocytes
Experimental Cell Research, 1997Co-Authors: Krista L Hess, Kim Sue R S Tudor, Jacob D Johnson, Farzaneh Osatiashtiani, David S Askew, Joan M CookmillsAbstract:Abstract Apoptotic cell death occurs during normal Lymphocyte development and differentiation as well as following Lymphocyte exposure to endogenous corticosteroids released during stress, malnutrition, and trauma. Recognition and engulfment of these apoptotic cells is important for the clearance of dying cells before they release potent inflammatory mediators into the vasculature or tissues. Phagocytosis of apoptotic cells is accomplished in part by macrophages. We report for the first time that apoptotic Lymphocytes are also phagocytosed by high endothelial venule (HEV) cells. The murine HEV cell line mHEVa rapidly phagocytosed apoptotic lymphoid and myeloid cells with the greatest rate of phagocytosis occurring at 0–6 h. To confirm HEV cell interaction with apoptotic cells, we demonstrated that apoptotic human tonsil Lymphocytes were phagocytosed by human tonsil HEV cells in primary cultures. Furthermore, we examined HEV cell phagocytosisin vivo.Mice were treated with a natural corticosterone (4-pregnene-11β,21-diol-3,20-dione) at levels detected during stress or malnutrition (93–180 μg serum cortisol/dl). At 4–12 h posttreatment, apoptotic Lymphocytes were present inside vacuoles of HEV cells in axillary lymph node tissue sections, as determined by transmission electron microscopy. These data suggest that, in addition to macrophages, lymph node HEV cells also play a role in the removal of apoptotic Lymphocytes. Moreover, since HEV cells are specialized endothelial cells that regulate Lymphocyte migration into peripheral lymphoid tissues, they may provide an important checkpoint for clearance of apoptotic Lymphocytes within the vasculature, as well as limiting entrance of nonfunctional Lymphocytes into the lymph node.
David A Cooper - One of the best experts on this subject based on the ideXlab platform.
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alterations in the immune response of human immunodeficiency virus hiv infected subjects treated with an hiv specific protease inhibitor ritonavir
The Journal of Infectious Diseases, 1996Co-Authors: Anthony D Kelleher, Andrew Carr, John Zaunders, David A CooperAbstract:: Effects of a human immunodeficiency virus (HIV) type 1 protease inhibitor, ritonavir, were evaluated in 21 patients enrolled in a phase I/II study. The magnitude and rates of CD4 and CD8 Lymphocyte increase, changes in subsets of CD4 and CD8 Lymphocytes, and proliferative responses to mitogen and antigens were analyzed. Significant increases were noted in CD4 and CD8 Lymphocyte counts; numbers of CD4CD45RO Lymphocytes increased significantly by week 1 of therapy. Increases in the CD4CD45RA subset were observed at week 4. Reductions in the percentage of CD4 and CD8 Lymphocytes expressing CD38 were noted. Increases in proliferative responses to phytohemagglutinin were noted in 6 of 7 patients and correlated with duration of virus load suppression. Increased responses to recall antigens and to HIV-specific proteins were observed. Treatment with ritonavir produced alterations in the immune system that included changes in T cell subset distribution and increases in CD4 and CD8 Lymphocyte numbers and of Lymphocyte function.
Huijuan Yang - One of the best experts on this subject based on the ideXlab platform.
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clinical significance of peripheral blood and tumor tissue Lymphocyte subsets in cervical cancer patients
BMC Cancer, 2020Co-Authors: Yutuan Wu, Shuang Ye, Shyamal Goswami, Libing Xiang, Xiaoming Zhang, Huijuan YangAbstract:Alterations in peripheral blood Lymphocytes in cervical cancer have been reported, although conflicting views exist. The present study investigated the distributions of Lymphocyte subsets in tumor tissue and peripheral blood samples from cervical cancer patients and precancerous lesion patients, and evaluated the correlations of Lymphocyte subsets with clinicopathological and prognostic variables. A total of 44 patients with stage IB1-IIA2 cervical cancer and 13 precancerous lesion patients were included. Lymphocytes were collected from the tumor tissue and the peripheral blood, and isolated by Lymphoprep density gradient centrifugation. The percentages of Lymphocyte subsets were quantified by flow cytometry analysis, and the differences between Lymphocyte subsets in the tumor tissue and peripheral blood were compared by SPSS. In addition, the relationships between Lymphocyte subsets and clinicopathological and prognostic variables were analyzed. Our results revealed that the amount of total T Lymphocytes, CD8+ T cells, granulocytes, pDCs, CD16+ monocytes and CD56high NK cells were significantly higher in the tumor tissue than in the peripheral blood in the cervical cancer patients, while those of CD4+ T cells, CD4+/CD8+ cell ratio, rdT cells, BDCA1+ mDCs, total monocytes, CD14+ monocytes, NK cells and CD56low NK cells exhibited the opposite trend (p < 0.05). The levels of total pDCs and BDCA1+ mDCs in the peripheral blood were significantly lower in the cervical cancer patients than in the precancerous lesion patients, while the proportion of CD16+ monocytes was elevated (p < 0.05). In addition, some Lymphocyte subsets, especially CD4+ cells and CD8+ cells, and the CD4+/CD8+ cell ratio were closely associated with clinicopathological and prognostic parameters. These results suggested that distinct alterations in infiltrating Lymphocyte subsets occurred in the tumor and were associated with clinicopathological and prognostic parameters. Systemic impairment of the immune system may occur in the antitumor response of cervical cancer patients.
Christine Moussion - One of the best experts on this subject based on the ideXlab platform.
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dendritic cells control Lymphocyte entry to lymph nodes through high endothelial venules
Nature, 2011Co-Authors: Christine Moussion, Jeanphilippe GirardAbstract:Christine Moussion and Jean-Philippe Girard report that dendritic cells in the immune system have an unexpected immune surveillance role in Lymphocyte recirculation during homeostasis. Lymphotoxin ligands derived from dendritic cells promote the growth of high endothelial venules — blood vessels specialized in Lymphocyte recruitment — which control the entry of naive Lymphocytes from the blood into lymph nodes. While patrolling the body in search of foreign antigens, naive Lymphocytes continuously circulate from the blood, through the lymph nodes, into the lymphatic vessels and back to the blood1,2. This process, called Lymphocyte recirculation, provides the body with effective immune surveillance for foreign invaders and for alterations to the body’s own cells. However, the mechanisms that regulate Lymphocyte recirculation during homeostasis remain incompletely characterized. Here we show that dendritic cells (DCs), which are well known for their role in antigen presentation to T Lymphocytes3, control the entry of naive Lymphocytes to lymph nodes by modulating the phenotype of high endothelial venules (HEVs), which are blood vessels specialized in Lymphocyte recruitment2,4,5. We found that in vivo depletion of CD11c+ DCs in adult mice over a 1-week period induces a reduction in the size and cellularity of the peripheral and mucosal lymph nodes. In the absence of DCs, the mature adult HEV phenotype reverts to an immature neonatal phenotype, and HEV-mediated Lymphocyte recruitment to lymph nodes is inhibited. Co-culture experiments showed that the effect of DCs on HEV endothelial cells is direct and requires lymphotoxin-β-receptor-dependent signalling. DCs express lymphotoxin, and DC-derived lymphotoxin is important for Lymphocyte homing to lymph nodes in vivo. Together, our results reveal a previously unsuspected role for DCs in the regulation of Lymphocyte recirculation during immune surveillance.
