Lymphocytes perform reverse adhesive haptotaxis mediated by LFA-1 integrins

Cell Guidance by anchored molecules, or haptotaxis, is crucial in development, immunology and cancer. Adhesive haptotaxis, or guidance by adhesion molecules, is well established for mesenchymal cells like fibroblasts, whereas its existence remains unreported for amoeboid cells that require less or no adhesion to migrate. We show here in vitro that amoeboid human T lymphocytes develop adhesive haptotaxis versus densities of integrin ligands expressed by high endothelial venules. Moreover, lymphocytes orient towards increasing adhesion with VLA-4 integrins, like all mesenchymal cells, but towards decreasing adhesion with LFA-1 integrins, which has never been observed. This counterintuitive ‘reverse haptotaxis’ cannot be explained with the existing mesenchymal mechanisms of competition between cells’ pulling edges or of lamellipodia growth activated by integrins, which favor orientation towards increasing adhesion. Mechanisms and functions of amoeboid adhesive haptotaxis remain unclear, however multidirectional integrin-mediated haptotaxis may operate around transmigration ports on endothelium, stromal cells in lymph nodes, and inflamed tissue where integrin ligands are spatially modulated.