Phillips, Rhian and Ager, Ann ![]() |
Abstract
In this study we examined the role of chemokines in regulating T lymphocyte transmigration across the lining high endothelial cells (HEC) of high endothelial venules (HEV). The roles played byCCL21 (SLC), CCL19 (MIP-3β, ELC) and CXCL12 (SDF-1) were assessed using an in vitro transendothelial migration culture system, which constitutively supports high levels of lymphocyte transmigration. We determined that transmigration of T lymphocytes across HEC is inhibitable by treatment of the T lymphocytes with pertussis toxin (PTX) (80% inhibition). This was attributed to blockade of Gi-protein coupled receptors of T lymphocytes, since a non-ADP-ribosylating form of PTX had no significant effect on transendothelial migration. Inhibition of Gi-protein-coupled receptors onthe endothelium had no effect on T cell transmigration. Treatment of T lymphocytes with a desensitizing concentration of CXCL12 caused a 60% reduction in T lymphocyte migration across HEC, and the CXCR4 antagonist SDF-1P2G reduced transmigration by 40%. Desensitizing concentrations of CCL21 and CCL19 had no significant effects on T lymphocyte transendothelial migration. Homologous desensitization of T lymphocytes to each chemokine was confirmed in a transwell migration assay. An approximately 3-kb mRNA corresponding to rat SDF-1β was constitutively expressed in HEC and cell surface CXCL12was detectable by enzyme-linked immunosorbent assay. Together, these findings support a pivotal role for HEC-expressed CXCL12 and its receptor on T cells in the regulation of T lymphocyte homing tolymph nodes.
Item Type: | Article |
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Date Type: | Publication |
Status: | Published |
Schools: | Medicine Systems Immunity Research Institute (SIURI) |
Subjects: | Q Science > QR Microbiology > QR180 Immunology |
Uncontrolled Keywords: | chemokine ; T lymphocyte ; high endothelial cell ; transendothelial migration |
Publisher: | Wiley-Blackwell |
ISSN: | 0014-2980 |
Last Modified: | 20 Oct 2022 09:51 |
URI: | https://orca.cardiff.ac.uk/id/eprint/33331 |
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