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

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.

• Authors: James A Deane, Latasha D Abeynaike, M Ursula Norman, Janet L Wee, A Richard Kitching, Paul Kubes, Michael J Hickey
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 188 Issue 5 Pg. 2179-88 (Mar 01 2012) ISSN: 1550-6606 [Electronic] United States
• PMID: 22279104 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Icam1 protein, mouse
• Intercellular Adhesion Molecule-1

Topics

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