Cutting Edge: Skin CCR10+ CD8+ T Cells Support Resident Regulatory T Cells through the B7.2/Receptor Axis To Regulate Local Immune Homeostasis and Response

J Immunol. 2016 Jun 15;196(12):4859-64. doi: 10.4049/jimmunol.1502662. Epub 2016 May 9.

Abstract

Resident T cells in barrier tissues are important in protecting against foreign agents but can also contribute to inflammatory diseases if dysregulated. How T cell homeostasis is maintained in barrier tissues is still poorly understood. We report that resident CD8(+) T cells directly support maintenance of regulatory T cells (Tregs) in the skin to promote immune homeostasis. Impaired establishment of resident CD8(+) T cells caused by knockout of the skin-homing chemokine receptor CCR10 resulted in an altered balance of resident Tregs and CD4(+) effector T cells in the skin and overreactive inflammatory responses to cutaneous stimulations. Furthermore, B7.2 expressed on skin CD8(+) T cells supports the survival of Tregs, likely through interaction with its receptor CTLA-4, which is highly expressed on skin Tregs. Our findings provide novel insights into T cell homeostatic regulation in the skin and may improve our understanding of the pathobiology of tissue inflammatory diseases.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • B7-2 Antigen / genetics
  • B7-2 Antigen / immunology
  • B7-2 Antigen / metabolism*
  • CD8-Positive T-Lymphocytes / immunology*
  • CTLA-4 Antigen / genetics
  • Gene Expression Regulation
  • Homeostasis
  • Inflammation / immunology
  • Mice
  • Receptors, CCR10 / genetics
  • Receptors, CCR10 / immunology*
  • Skin / cytology*
  • Skin / immunology*
  • Skin / pathology
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • B7-2 Antigen
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Receptors, CCR10