Accumulation of metal-specific T cells in inflamed skin in a novel murine model of chromium-induced allergic contact dermatitis

PLoS One. 2014 Jan 20;9(1):e85983. doi: 10.1371/journal.pone.0085983. eCollection 2014.

Abstract

Chromium (Cr) causes delayed-type hypersensitivity reactions possibly mediated by accumulating T cells into allergic inflamed skin, which are called irritants or allergic contact dermatitis. However, accumulating T cells during development of metal allergy are poorly characterized because a suitable animal model is not available. This study aimed to elucidate the skewing of T-cell receptor (TCR) repertoire and cytokine profiles in accumulated T cells in inflamed skin during elucidation of Cr allergy. A novel model of Cr allergy was induced by two sensitizations of Cr plus lipopolysaccharide solution into mouse groin followed by single Cr challenge into the footpad. TCR repertoires and nucleotide sequences of complementary determining region 3 were assessed in accumulated T cells from inflamed skin. Cytokine expression profiles and T-cell phenotypes were determined by qPCR. CD3+CD4+ T cells accumulated in allergic footpads and produced increased T helper 1 (Th1) type cytokines, Fas, and Fas ligand in the footpads after challenge, suggesting CD4+ Th1 cells locally expanded in response to Cr. Accumulated T cells included natural killer (NK) T cells and Cr-specific T cells with VA11-1/VB14-1 usage, suggesting metal-specific T cells driven by invariant NKT cells might contribute to the pathogenesis of Cr allergy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromium*
  • Cytokines / immunology
  • Dermatitis, Allergic Contact / etiology
  • Dermatitis, Allergic Contact / immunology*
  • Dermatitis, Allergic Contact / pathology
  • Disease Models, Animal*
  • Female
  • Mice / immunology*
  • Mice, Inbred BALB C
  • Receptors, Antigen, T-Cell / immunology*
  • Skin / immunology
  • Skin / pathology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / pathology

Substances

  • Cytokines
  • Receptors, Antigen, T-Cell
  • Chromium

Grants and funding

This study was supported by a Grant-in-Aid for Scientific Research C 70373470, and 23593004 from the Ministry of Education, Culture, Sports, Science and Technology, Japan (Y.H. and R.S.); and by Grants-in-Aid for Scientific Research from the Ministry of Health, Labour and Welfare of Japan H22-meneki-ippan-004 (K.O. and R.S.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.