CCR7 ligands control basal T cell motility within lymph node slices in a phosphoinositide 3-kinase-independent manner.
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.
Asperti-Boursin
François
F
Institut Cochin, Université Paris Descartes, Centre National de la Recherche Scientifique (UMR 8104), Paris, France.
Real
Eliana
E
Bismuth
Georges
G
Trautmann
Alain
A
Donnadieu
Emmanuel
E
D019264:Adoptive Transfer; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008024:Ligands; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D037342:Pertussis Toxin / Q000633:toxicity; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D054400:Receptors, CCR7 / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014162:Transfection
C515370:CCR7 protein, human; D008024:Ligands; D054400:Receptors, CCR7; D037342:Pertussis Toxin; D019869:Phosphatidylinositol 3-Kinases; D002118:Calcium