Perivascular leukocyte clusters are essential for efficient activation of effector T cells in the skin

Nat Immunol. 2014 Nov;15(11):1064-9. doi: 10.1038/ni.2992. Epub 2014 Sep 21.


It remains largely unclear how antigen-presenting cells (APCs) encounter effector or memory T cells efficiently in the periphery. Here we used a mouse contact hypersensitivity (CHS) model to show that upon epicutaneous antigen challenge, dendritic cells (DCs) formed clusters with effector T cells in dermal perivascular areas to promote in situ proliferation and activation of skin T cells in a manner dependent on antigen and the integrin LFA-1. We found that DCs accumulated in perivascular areas and that DC clustering was abrogated by depletion of macrophages. Treatment with interleukin 1α (IL-1α) induced production of the chemokine CXCL2 by dermal macrophages, and DC clustering was suppressed by blockade of either the receptor for IL-1 (IL-1R) or the receptor for CXCL2 (CXCR2). Our findings suggest that the dermal leukocyte cluster is an essential structure for elicitating acquired cutaneous immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD11c Antigen / genetics
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Proliferation
  • Chemokine CXCL2 / biosynthesis
  • Dendritic Cells / immunology*
  • Dermatitis, Contact / immunology*
  • Female
  • Immunologic Memory / immunology
  • Interleukin-1alpha / pharmacology
  • Lymphocyte Activation / immunology
  • Lymphocyte Function-Associated Antigen-1 / immunology
  • Macrophages / cytology
  • Macrophages / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Animal
  • Neutrophils / immunology
  • Receptors, Interleukin-1 / antagonists & inhibitors
  • Receptors, Interleukin-8B / antagonists & inhibitors
  • Skin / immunology*
  • Skin / pathology


  • CD11c Antigen
  • Chemokine CXCL2
  • Cxcl2 protein, mouse
  • Interleukin-1alpha
  • Lymphocyte Function-Associated Antigen-1
  • Receptors, Interleukin-1
  • Receptors, Interleukin-8B