The T cell chemokine receptor CCR7 is internalized on stimulation with ELC, but not with SLC.
ELC and SLC are potent agonists for CCR7, a receptor of up-most importance for the regulation of the homing and traffic of lymphocytes into and within secondary lymphoid tissues. We have studied the effects of both chemokines on receptor re-distribution in T lymphocytes and other CCR7-bearing cells by flow cytometry and by assessing receptor mediated functions. In this paper we show that ELC and SLC differ fundamentally in the ability to induce the internalization of their receptor. ELC induced a rapid time- and concentration-dependent internalization of CCR7 and markedly decreased the ability of CCR7-bearing cells to respond to a second stimulation. No receptor internalization, by contrast, was observed on stimulation with SLC. Receptors that were internalized on stimulation with ELC were re-expressed when the cells were washed. Re-expression of receptors and consequent re-activation of the cells was prevented in the presence of ELC, but was not affected in the presence of SLC. These findings could explain how T lymphocytes that enter lymphoid tissues in response to SLC produced by high-endothelial venules can subsequently migrate in response to SLC and ELC expressed within the T cell areas.
Bardi
G
G
Theodor-Kocher Institute, University of Bern, Bern, Switzerland.
Lipp
M
M
Baggiolini
M
M
Loetscher
P
P
D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D018925:Chemokines / Q000494:pharmacology*; D006801:Humans; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism
C515370:CCR7 protein, human; D018925:Chemokines; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D002118:Calcium