Identification and Characterization of Circulating Naïve CD4+ and CD8+ T Cells Recognizing Nickel

Front Immunol. 2019 Jun 12;10:1331. doi: 10.3389/fimmu.2019.01331. eCollection 2019.

Abstract

Allergic contact dermatitis caused by contact sensitizers is a T-cell-mediated inflammatory skin disease. The most prevalent contact allergens is nickel. Whereas, memory T cells from nickel-allergic patients are well-characterized, little is known concerning nickel-specific naïve T-cell repertoire. The purpose of this study was to identify and quantify naïve CD4+ and CD8+ T cells recognizing nickel in the general population. Using a T-cell priming in vitro assay based on autologous co-cultures between naïve T cells and dendritic cells loaded with nickel, we were able to detect a naïve CD4+ and CD8+ T-cell repertoire for nickel in 10/11 and 7/8 of the tested donors. We calculated a mean frequency of 0.49 nickel-specific naïve CD4+ T cells and 0.37 nickel-specific naïve CD8+ T cells per million of circulating naïve T cells. The activation of these specific T cells requires MHC molecules and alongside IFN-γ production, some nickel-specific T-cells were able to produce granzyme-B. Interestingly, nickel-specific naïve CD4+ and CD8+ T cells showed a low rate of cross-reactivity with cobalt, another metallic hapten, frequently mixed with nickel in many alloys. Moreover, naïve CD4+ T cells showed a polyclonal TCRβ composition and the presence of highly expanded clones with an enrichment and/or preferentially expansion of some TRBV genes that was donor and T-cell specific. Our results contribute to a better understanding of the mechanism of immunization to nickel and propose the T-cell priming assay as a useful tool to identify antigen-specific naïve T cells.

Keywords: T-cell assay; allergic contact dermatitis; allergy and immunology; in vitro tests; metals hapten; naive T cells; repertoire.

MeSH terms

  • Blood Circulation
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cells, Cultured
  • Clone Cells
  • Dermatitis, Allergic Contact / immunology*
  • Enzyme-Linked Immunospot Assay
  • Genes, T-Cell Receptor beta / genetics
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Immunophenotyping
  • Interferon-gamma / metabolism
  • Lymphocyte Activation
  • Nickel
  • T-Cell Antigen Receptor Specificity

Substances

  • Nickel
  • Interferon-gamma