P-SELECTIN GLYCOPROTEIN LIGAND-1 (PSGL-1) ON T-HELPER-1 BUT NOT ON T-HELPER-2 CELLS BINDS TO P-SELECTIN AND SUPPORTS MIGRATION INTO INFLAMED SKIN

We have shown recently that mouse Th1 cells but not Th2 cells are sele ctively recruited into inflamed sites of a delayed-type hypersensitivi ty (DTH) reaction of the skin. This migration was blocked by monoclona l antibodies (mAb) against P- and E-selectin. Here we show that Th1 ce lls bind to P-selectin via the P-selectin glycoprotein ligand-1 (PSGL- 1). This is the only glycoprotein ligand that was detectable by affini ty isolation with a P-selectin-Ig fusion protein. Binding of Th1 cells to P-selectin, as analyzed by now cytometry and in cell adhesion assa ys, was completely blocked by antibodies against PSGL-1. The same anti bodies blocked partially the migration of Th1 cells into cutaneous DTH reactions. This blocking activity, in combination with that of a mAb against E-selectin, was additive. PSGL-1 on Th2 cells, although expres sed at similar levels as on Th1 cells, did not support binding to P-se lectin. Thus, the P-selectin-binding form of PSGL-1 distinguishes Th1 cells from Th2 cells. Furthermore, PSGL-1 is relevant for the entry of Th1 cells into inflamed areas of the skin. This is the first demonstr ation for the importance of PSGL-1 for mouse leukocyte recruitment in vivo.