Crawling T lymphocytes are guided by Flow

M Biarnes-Pelicot, A Lellouch, O Theodoly, MP Valignat. Collaboration with Nancy Hogg (UK Cancer research)

In leaving the blood stream for lymph nodes or sites of inflammation, T lymphocytes are captured by the endothelium and migrate along the vascular wall to permissive sites of transmigration. These processes take place under the influence of hemodynamic shear stress and we investigated here how migrational speed and directionality are influenced by variations in shear stress. Naive and effector T lymphocytes and neutrophils, have been examined on ICAM-1 coated surfaces under the influence of shear stresses from 2 to 60 We found that the speed of both T lymphocytes and neutrophils was shear stress independent. However, the entire T lymphocyte population responded to shear stress by a rapid (30 s) and fully reversible orientation of their migration against the direction of fluid flow, while the population of neutrophils and leukemic HSB2 T lymphocytes oriented their migration with the direction of fluid flow. These results suggest that there exist fundamental differences in the migratory mechanisms of the different classes of leucocytes responsible for the innate and adaptive immune response. Our findings also suggest that abnormal vascular architecture or certain leukocyte malignancies could contribute to the dysregulation of the extravasation process.

Figure 3 : Effector T lymphocyte crawl against a flow. A- Image of a lymphocyte crawling against a flow of 8 dyn/cm2. The yellow arrow shows flow direction. B- Mean square displacement of cells versus time in absence (yellow) and presence (blue) of flow, showing a clear transition between diffusive and ballistic motions.