Format

Send to

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

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

Author information

1
1] Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan. [2] Department of Dermatology, Kurume University School of Medicine, Fukuoka, Japan.
2
Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
3
Research Unit for Immunodynamics, RIKEN Research Center for Allergy and Immunology, Kanagawa, Japan.
4
Department of Pharmaceutical Biochemistry, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
5
1] Laboratory of Adjuvant Innovation, National Institute of Biomedical Innovation, Osaka, Japan. [2] Laboratory of Vaccine Science, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan.
6
Department of Microbiology, Hyogo College of Medicine, Hyogo, Japan.
7
Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan.
8
1] Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan. [2] Medical Mycology Research Center, Chiba University, Chiba, Japan.
9
1] Laboratory for Cytokine Regulation, RIKEN center for Integrative Medical Science, Kanagawa, Japan. [2] Division of Molecular Pathology, Research Institute for Biomedical Science, Tokyo University of Science, Chiba, Japan.
10
Singapore Immunology Network, Agency for Science, Technology and Research, Biopolis, Singapore.
11
Department of Dermatology, Kurume University School of Medicine, Fukuoka, Japan.
12
Department of Dermatology, Icahn School of Medicine at Mount Sinai School Medical Center, New York, New York,.

Abstract

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.

PMID:
25240383
DOI:
10.1038/ni.2992
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for Kyoto University Research Information Repository - Articles
Loading ...
Support Center