title: Both Th1 and Th2 cells require P-selectin glycoprotein ligand-1 for optimal rolling on inflamed endothelium.
abstract: The acquisition of homing receptors that redirect lymphocyte trafficking to nonlymphoid tissues after antigen encounter is a fundamental aspect of effector T-cell development. Although a role for selectins and their ligands has been well characterized for trafficking of Th1 cells to nonlymphoid sites, mechanisms responsible for Th2 trafficking are not well understood. Using a flow chamber system in which the endothelial interactions of two distinct T-cell populations could be examined simultaneously, we directly compared the requirements for Th1 and Th2 cell tethering and rolling. We found that although Th2 cells expressed significantly lower levels of selectin ligands than Th1 cells, activation of the endothelium by Th2-derived factors induced rolling interactions that were comparable for both Th1 and Th2 populations. Further, in the absence of PSGL-1, no other adhesion molecule could effectively compensate for lack of PSGL-1 to mediate rolling of either Th1 or Th2 cells. Thus, both Th1 and Th2 populations express functional PSGL-1-based selectin ligands for tethering and rolling on activated endothelium, and both effector populations can use PSGL-1 as the dominant scaffold for functional selectin ligand expression.
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, USA.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Mangan
authors.forename: Darrell
authors.initials: D
authors.lastname: O'Quinn
authors.forename: Laurie
authors.initials: L
authors.lastname: Harrington
authors.forename: Claudine S
authors.initials: CS
authors.lastname: Bonder
authors.forename: Paul
authors.initials: P
authors.lastname: Kubes
authors.forename: Dennis F
authors.initials: DF
authors.lastname: Kucik
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Bullard
authors.forename: Casey T
authors.initials: CT
authors.lastname: Weaver
mesh_terms: D000818:Animals; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005434:Flow Cytometry; D007249:Inflammation; D036904:Leukocyte Rolling / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D018417:Th1 Cells / Q000187:drug effects / Q000502:physiology*; D018418:Th2 Cells / Q000187:drug effects / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D011948:Receptors, Antigen, T-Cell; D014409:Tumor Necrosis Factor-alpha