Gollmer, Kathrin; Asperti-Boursin, François; Tanaka, Yoshihiko; Okkenhaug, Klaus; Vanhaesebroeck, Bart; Peterson, Jeffrey R; Fukui, Yoshinori; Donnadieu, Emmanuel; Stein, Jens V (2009). CCL21 mediates CD4+ T-cell costimulation via a DOCK2/Rac-dependent pathway. Blood, 114(3), pp. 580-8. Washington, D.C.: American Society of Hematology 10.1182/blood-2009-01-200923
Full text not available from this repository.CD4(+) T cells use the chemokine receptor CCR7 to home to and migrate within lymphoid tissue, where T-cell activation takes place. Using primary T-cell receptor (TCR)-transgenic (tg) CD4(+) T cells, we explored the effect of CCR7 ligands, in particular CCL21, on T-cell activation. We found that the presence of CCL21 during early time points strongly increased in vitro T-cell proliferation after TCR stimulation, correlating with increased expression of early activation markers. CCL21 costimulation resulted in increased Ras- and Rac-GTP formation and enhanced phosphorylation of Akt, MEK, and ERK but not p38 or JNK. Kinase-dead PI3Kdelta(D910A/D910A) or PI3Kgamma-deficient TCR-tg CD4(+) T cells showed similar responsiveness to CCL21 costimulation as control CD4(+) T cells. Conversely, deficiency in the Rac guanine exchange factor DOCK2 significantly impaired CCL21-mediated costimulation in TCR-tg CD4(+) T cells, concomitant with impaired Rac- but not Ras-GTP formation. Using lymph node slices for live monitoring of T-cell behavior and activation, we found that G protein-coupled receptor signaling was required for early CD69 expression but not for Ca(2+) signaling. Our data suggest that the presence of CCL21 during early TCR signaling lowers the activation threshold through Ras- and Rac-dependent pathways leading to increased ERK phosphorylation.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute |
UniBE Contributor: |
Gollmer, Kathrin, Stein, Jens Volker |
ISSN: |
0006-4971 |
Publisher: |
American Society of Hematology |
Language: |
English |
Submitter: |
Factscience Import |
Date Deposited: |
04 Oct 2013 15:13 |
Last Modified: |
05 Dec 2022 14:22 |
Publisher DOI: |
10.1182/blood-2009-01-200923 |
PubMed ID: |
19451552 |
Web of Science ID: |
000268061800017 |
URI: |
https://boris.unibe.ch/id/eprint/32156 (FactScience: 197085) |
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