P-, E-, and L-selectin mediate migration of activated CD8+ T lymphocytes into inflamed skin

J Immunol. 2002 Oct 15;169(8):4307-13. doi: 10.4049/jimmunol.169.8.4307.

Abstract

P- and E-selectin mediate CD4+ Th1 cell migration into the inflamed skin in a murine contact hypersensitivity model. In this model, not only CD4+ T cells but also CD8+ T cells infiltrate the inflamed skin, and the role of CD8+ type 1 cytotoxic T (Tc1) cells as effector cells has been demonstrated. Here we show that in mice deficient in both P- and E-selectin, the infiltration of CD8+ T cells in the inflamed skin is reduced, suggesting the role of these selectins in CD8+ T cell migration. We directly studied the role of selectins using in vitro-generated Tc1 cells. These cells are able to migrate into the inflamed skin of wild-type mice. This migration is partially mediated by P- and E-selectin, as shown by the reduced Tc1 cell migration into the inflamed skin of mice deficient in both P- and E-selectin or wild-type mice treated with the combination of anti-P-selectin and anti-E-selectin Abs. During P- and E-selectin-mediated migration of Tc1 cells, P-selectin glycoprotein ligand-1 appears to be the sole ligand for P-selectin and one of the ligands for E-selectin. P- and E-selectin-independent migration of Tc1 cells into the inflamed skin was predominantly mediated by L-selectin. These observations indicate that all three selectins can mediate Tc1 cell migration into the inflamed skin.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / pathology*
  • Cell Adhesion / genetics
  • Cell Adhesion / immunology
  • Cell Movement / genetics
  • Cell Movement / immunology*
  • Dermatitis, Contact / genetics
  • Dermatitis, Contact / immunology*
  • Dermatitis, Contact / pathology*
  • Disease Models, Animal
  • Down-Regulation / genetics
  • Down-Regulation / immunology
  • E-Selectin / genetics
  • E-Selectin / metabolism
  • E-Selectin / physiology
  • L-Selectin / physiology
  • Ligands
  • Lymphocyte Activation* / genetics
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • P-Selectin / genetics
  • P-Selectin / metabolism
  • P-Selectin / physiology
  • Selectins / genetics
  • Selectins / metabolism
  • Selectins / physiology*
  • Skin / immunology
  • Skin / pathology*
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / pathology

Substances

  • E-Selectin
  • Ligands
  • Membrane Glycoproteins
  • P-Selectin
  • P-selectin ligand protein
  • Selectins
  • L-Selectin