CCL21 mediates CD4+ T-cell costimulation via a DOCK2/Rac-dependent pathway
Kathrin Gollmer1, François Asperti-Boursin, Yoshihiko Tanaka
1Theodor Kocher Institute, University of Bern, Freiestrasse 1, Bern, Switzerland.
Blood
|May 20, 2009
Summary
Chemokine CCL21 enhances T-cell activation by lowering the activation threshold through Ras- and Rac-dependent pathways. This chemokine receptor CCR7 signaling boosts T-cell proliferation and early activation marker expression.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- CD4(+) T cells utilize the CCR7 chemokine receptor for homing and migration within lymphoid tissues.
- Lymphoid tissue is a critical site for T-cell activation and immune responses.
Purpose of the Study:
- To investigate the impact of the CCR7 ligand CCL21 on T-cell activation.
- To elucidate the molecular pathways involved in CCL21-mediated costimulation of T cells.
Main Methods:
- Utilized primary T-cell receptor (TCR)-transgenic (tg) CD4(+) T cells for in vitro studies.
- Employed lymph node slices for live monitoring of T-cell behavior and activation.
- Assessed GTP formation (Ras, Rac) and protein phosphorylation (Akt, MEK, ERK, p38, JNK).
Main Results:
- CCL21 significantly increased T-cell proliferation and early activation marker expression upon TCR stimulation.
- CCL21 costimulation enhanced Ras- and Rac-GTP formation and Akt, MEK, and ERK phosphorylation.
- DOCK2 deficiency impaired CCL21-mediated costimulation, highlighting the role of Rac signaling.
Conclusions:
- CCL21 lowers the T-cell activation threshold during early TCR signaling.
- Ras- and Rac-dependent pathways, leading to ERK phosphorylation, are crucial for CCL21-mediated costimulation.
- G protein-coupled receptor signaling is essential for early CD69 expression in T cells.
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