CD4+ T cells migrate into inflamed skin only if they express ligands for E- and P-selectin.
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 induced in vivo upon skin sensitization, using soluble selectin-Ig chimera and blocking Abs. Only low numbers of CD4+ cells expressing significant levels of E- or P-selectin ligands were present in s.c. lymph nodes 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 judged 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-selectin-binding CD4+ cells, isolated by FACS, efficiently migrated into inflamed, but not normal skin, whereas P- or E-selectin ligand-negative CD4+ T cells did not. Abs against one of the two endothelial selectins 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 functional ligands for E- and for P-selectin is essential for homing of CD4+ T cells into the inflamed skin.
Department of Immunology, Medical Clinic, University Hospital Eppendorf, Hamburg, Germany.
W
W
Tietz
Y
Y
Allemand
E
E
Borges
D
D
von Laer
R
R
Hallmann
D
D
Vestweber
A
A
Hamann
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002465:Cell Movement / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D003877:Dermatitis, Contact / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019040:E-Selectin / Q000378:metabolism* / Q000502:physiology; D005260:Female; D016130:Immunophenotyping; D007399:Interphase / Q000276:immunology; D008024:Ligands; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D019007:P-Selectin / Q000378:metabolism* / Q000502:physiology; D011485:Protein Binding / Q000276:immunology; D012867:Skin / Q000276:immunology / Q000473:pathology; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism
D016207:Cytokines; D019040:E-Selectin; D008024:Ligands; D019007:P-Selectin