Endogenous regulatory T cells adhere in inflamed dermal vessels via ICAM-1: association with regulation of effector leukocyte adhesion

J Immunol. 2012 Mar 1;188(5):2179-88. doi: 10.4049/jimmunol.1102752. Epub 2012 Jan 25.

Abstract

Regulatory T cells (Tregs) must express appropriate skin-homing adhesion molecules to exert suppressive effects on dermal inflammation. However, the mechanisms whereby they control local inflammation remain unclear. In this study we used confocal intravital microscopy in wild-type and Foxp3-GFP mice to examine adhesion of effector T cells and Tregs in dermal venules. These experiments examined a two-challenge model of contact sensitivity (CS) in which Treg abundance in the skin progressively increases during the course of the response. Adhesion of CD4(+) T cells increased during CS, peaking 8-24 h after an initial hapten challenge, and within 4 h of a second challenge. At these time points, 40% of adherent CD4(+) T cells were Foxp3(+) Tregs. CD4(+) T cell adhesion was highly dependent on ICAM-1, and consistent with this finding, anti-ICAM-1 prevented Treg adhesion. Skin TGF-β levels were elevated in skin during both challenges, in parallel with Treg adhesion. In the two-challenge CS model, inhibition of ICAM-1 eliminated Treg adhesion, an effect associated with a significant increase in neutrophil adhesion. Similarly, total CD4(+) T cell depletion caused an increase in adhesion of CD8(+) T cells. Because Treg adhesion was restricted by both of these treatments, these experiments suggest that adherent Tregs can control adhesion of proinflammatory leukocytes in vivo. Moreover, the critical role of ICAM-1 in Treg adhesion provides a potential explanation for the exacerbation of inflammation reported in some studies of ICAM-1-deficient mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion / genetics
  • Cell Adhesion / immunology
  • Dermatitis, Contact / genetics
  • Dermatitis, Contact / immunology*
  • Dermatitis, Contact / pathology
  • Inflammation / genetics
  • Inflammation / immunology
  • Inflammation / pathology
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / metabolism
  • Intercellular Adhesion Molecule-1 / physiology*
  • Leukocytes / immunology
  • Leukocytes / metabolism
  • Leukocytes / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Skin / blood supply*
  • Skin / immunology*
  • Skin / pathology
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • T-Lymphocytes, Regulatory / pathology*
  • Venules / immunology
  • Venules / metabolism
  • Venules / pathology

Substances

  • Icam1 protein, mouse
  • Intercellular Adhesion Molecule-1