CD4(-CELLS MIGRATE INTO INFLAMED SKIN ONLY IF THEY EXPRESS LIGANDS FOR E-SELECTIN AND P-SELECTIN() T)

Previous data suggested a role of endothelial selectins in skin homing of lymphocytes. In the current study, we have analyzed the expression and functional role of E- and P-selectin ligands on CD4(+) T cells in duced in vivo upon skin sensitization, using soluble selectin-Ig chime ra and blocking Abs, Only low numbers of CD4(+) cells expressing signi ficant levels of E- or P-selectin ligands were present in s.c. lymph n odes of untreated mice (0.5-1.5% and 2-4%, respectively). Induction of a delayed-type hypersensitivity reaction increased the percentage of E-selectin-binding CD4(+) cells in the draining lymph nodes up to 6 to 9% and that of P-selectin-binding cells up to 14%. The majority of E- and P-selectin-binding cells displayed an activated phenotype as judg ed by the increase in IL-2R, CD71, or cell size. The populations of E- and P-selectin-binding cells were largely overlapping; all E-selectin -binding cells also bound to P-selectin, whereas only a subfraction of P-selectin-binding cells reacted with E-selectin, Both E- and P-selec tin-binding CD4(+) cells, isolated by FAGS, efficiently migrated into inflamed, but not normal skin, whereas P- or E-selectin ligand-negativ e CD4(+) T cells did not. Abs against one of the two endothelial selec tins partially inhibited the entry of isolated, ligand-positive cells, whereas a combination of Abs against both selectins almost completely abrogated skin homing. These data indicate that the expression of fun ctional ligands for E- and for P-selectin is essential for homing of C D4(+) T cells into the inflamed skin.