RT Journal Article
SR Electronic
T1 Activated CD8 T cells express two distinct P-Selectin Ligands
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 167957
DO 10.1101/167957
A1 Douglas A. Carlow
A1 Michelle C. Tra
A1 Hermann J. Ziltener
YR 2017
UL http://biorxiv.org/content/early/2017/08/25/167957.abstract
AB P-selectin (PSel) expressed on activated endothelia and platelets supports recruitment of leukocytes expressing PSel ligand (PSelL) to sites of inflammation. While monitoring PSelL expression on activated CD8+ T cells (Tact) in adoptive transfer models, we observed two distinct PSelL on responding donor cells, the canonical cell-intrinsic PSelL PSGL1 and a second undocumented PSelL provisionally named PSL2. PSL2 is unusual among selectin ligands in that it is cell-extrinsic, loaded onto L-selectin (LSel) expressed by Tact but not LSel on resting naïve CD8+ T cells. PSL2 expression is highest on Tact responding in peripheral lymph nodes and low on Tact responding in spleen suggesting that the original source of PSL2 is high endothelial venules, cells known to produce LSelL. When both PSGL1 and PSL2 were absent from the surface of Tact, no significant residual PSelL activity was detected. PSL2 is a ligand for both PSel and LSel and can physically bridge the two selectins. The LSel/PSL2 complex can mediate PSel-dependent adherence of Tact to immobilized PSel-hIgG or to activated platelets, either independently or cooperatively with PSGL1. PSel engagement of PSGL1 and LSel/PSL2 would likely deliver distinct signals known to be relevant in leukocyte recruitment.One sentence summary Murine primary in-vivo activated CD8+ T cells express two ligands for P-selectin, canonical PSGL-1 and a cell-extrinsic ligand docked on L-selectin.