The molecular mechanisms responsible for the sustained basal motility of T cells within lymph nodes (LNs) remain elusive. To study T cell motility in a LN environment, we have developed a new experimental system based on slices of LNs that allows the assessment of T cell trafficking after adoptive transfer or direct addition of T cells to the slice. Using this experimental system, we show that T cell motility is highly sensitive to pertussis toxin and strongly depends on CCR7 and its ligands. Our results also demonstrate that, despite its established role in myeloid cell locomotion, phosphoinositide 3–kinase (PI3K) activity does not contribute to the exploratory behavior of the T lymphocytes within LN slices. Likewise, although PI3K activation is detectable in chemokine-treated T cells, PI3K plays only a minor role in T cell polarization and migration in vitro. Collectively, our results suggest that the common amplification system that, in other cells, facilitates large phosphatidylinositol 3,4,5-trisphosphate increases at the plasma membrane is absent in T cells. We conclude that T cell motility within LNs is not an intrinsic property of T lymphocytes but is driven in a PI3K-independent manner by the lymphoid chemokine-rich environment.
CCR7 ligands control basal T cell motility within lymph node slices in a phosphoinositide 3–kinase– independent manner
Abbreviations used: CCL and CCR, CC chemokine ligand and receptor, respectively; CMFDA, 5-chloromethylfluorescein diacetate; CXCL, CXC chemokine ligand; DOCK2, dedicator of cytokinesis 2; FRC, fibroblastic reticular cell; GEF, guanine nucleotide exchange factor; HEV, high endothelial venule; PBT cell, peripheral blood T cell; PH, pleckstrin homology; PI3K, phosphoinositide 3–kinase; PIP3, phosphatidylinositol 3,4,5-trisphosphate; plt, paucity of LN T cell; PTX, pertussis toxin; WMN, wortmannin.
F. Asperti-Boursin and E. Real contributed equally to this work.
François Asperti-Boursin, Eliana Real, Georges Bismuth, Alain Trautmann, Emmanuel Donnadieu; CCR7 ligands control basal T cell motility within lymph node slices in a phosphoinositide 3–kinase– independent manner . J Exp Med 14 May 2007; 204 (5): 1167–1179. doi: https://doi.org/10.1084/jem.20062079
Download citation file:
Sign in
Client Account
Sign in via your Institution
Sign in via your InstitutionEmail alerts
Advertisement