Immunohistochemical analysis of regulatory T cell markers FOXP3 and GITR on CD4+CD25+ T cells in normal skin and inflammatory dermatoses

J Histochem Cytochem. 2007 Sep;55(9):891-8. doi: 10.1369/jhc.6A7119.2007. Epub 2007 May 3.

Abstract

Regulatory T cells (Treg) are a subset of T lymphocytes that play a central role in immunologic tolerance and in the termination of immune responses. The identification of these cells in normal and inflammatory conditions may contribute to a better understanding of underlying pathology. We investigated the expression of FOXP3 and GITR in normal skin and in a panel of different inflammatory dermatoses. Immunohistochemical double stainings in skin tissue sections revealed that FOXP3 and GITR were almost exclusively present on T cells that express both CD4 and CD25. Further, immunohistochemical double staining, as well as fluorescence-activated cell sorter analysis, on peripheral blood T cells showed that most FOXP3(+) cells expressed GITR and vice versa, whereas a minority were single-positive for these markers. The mean frequency of FOXP3(+) T cells in spongiotic dermatitis, psoriasis, and lichen planus was in the same range (25-29%), but the frequency of these cells in leishmaniasis appeared to be lower (approximately 15%), although this was not statistically significant. The mean frequency of GITR(+) T cells was fairly similar in all conditions studied (14-20%). Normal human skin also contained FOXP3(+) and GITR(+) cells in the same frequency range as in diseased skin, but the absolute numbers were, of course, much lower. In conclusion, frequencies of FOXP3(+) and GITR(+) T cells were similar in all inflammatory skin diseases studied and normal skin, despite the well-known differences among the inflammatory conditions under investigation.

MeSH terms

  • Biomarkers / metabolism
  • CD4 Antigens / metabolism*
  • Dermatitis, Allergic Contact / immunology
  • Dermatitis, Allergic Contact / metabolism
  • Forkhead Transcription Factors / metabolism*
  • Glucocorticoid-Induced TNFR-Related Protein
  • Humans
  • Interleukin-2 Receptor alpha Subunit / metabolism*
  • Leishmaniasis / immunology
  • Leishmaniasis / metabolism
  • Lichen Planus / immunology
  • Lichen Planus / metabolism
  • Psoriasis / immunology
  • Psoriasis / metabolism
  • Receptors, Nerve Growth Factor / metabolism*
  • Receptors, Tumor Necrosis Factor / metabolism*
  • Skin / immunology*
  • Skin / metabolism
  • Skin Diseases / immunology*
  • Skin Diseases / metabolism
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism

Substances

  • Biomarkers
  • CD4 Antigens
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Glucocorticoid-Induced TNFR-Related Protein
  • Interleukin-2 Receptor alpha Subunit
  • Receptors, Nerve Growth Factor
  • Receptors, Tumor Necrosis Factor
  • TNFRSF18 protein, human