A cell-extrinsic ligand acquired by activated T cells in lymph node can bridge L-selectin and P-selectin

Douglas A. Carlow, Michelle C. Tra, Hermann J. Ziltener, Markus Sperandio
2018 PLoS ONE  
P-selectin expressed on activated endothelia and platelets supports recruitment of leukocytes expressing P-selectin ligand to sites of inflammation. While monitoring P-selectin ligand expression on activated CD8 + T cells in murine adoptive transfer models, we observed two distinct ligands on responding donor cells, the canonical cell-intrinsic P-selectin ligand PSGL-1 and a second undocumented P-selectin ligand we provisionally named PSL2. PSL2 is unusual among selectin ligands in that it is
more » ... nds in that it is cell-extrinsic, loaded onto L-selectin expressed by activated T cells but not L-selectin on resting naïve CD8 + T cells. PSL2 display is highest on activated T cells responding in peripheral lymph nodes and low on T cells responding in spleen suggesting that the original source of PSL2 is high endothelial venules, cells known to produce L-selectin ligands. PSL2 is a ligand for both P-selectin and L-selectin and can physically bridge the two selectins. The L-selectin/PSL2 complex can mediate Pselectin-dependent adherence of activated T cells to immobilized P-selectin or to activated platelets, either independently or cooperatively with PSGL-1. PSL2's capacity to bridge between L-selectin on activated T cells and P-selectin reveals an undocumented and unanticipated activity of cell-extrinsic selectin ligands in mediating selectin-selectin connectivity. The timing and circumstances of PSL2 detection on T cells, together with its capacity to support adherence to P-selectin-bearing substrates, are consistent with P-selectin engagement of both PSGL1 and the L-selectin/PSL2 complex during T cell recruitment. Engagement of PSGL-1 and L-selectin/PSL2 would likely deliver distinct signals known to be relevant in this process.
doi:10.1371/journal.pone.0205685 fatcat:rbz75kdz4fbeffacihmgwdeyh4