Immunohistochemical Analysis of Regulatory T Cell Markers FOXP3 and GITR on CD4+CD25+ T Cells in Normal Skin and Inflammatory Dermatoses
Onno J. de Boer 1*, Chris M. van der Loos 1, Peter Teeling 1, Allard C. van der Wal 1 and Marcel B.M. Teunissen 1
1 Departments of Pathology (OJdB,CMvdL,PT,ACvdW) and Dermatology (MBMT), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
* To whom correspondence should be addressed. E-mail: o.j.deboer{at}amc.uva.nl.
Submitted on October 18, 2006
Accepted on 9 April 2007
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Abstract |
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Regulatory T cells (Treg) are a subset of T lymphocytes that play a central role in immunologic tolerance and the termination of immune responses. The identification of these cells in normal and inflammatory conditions may contribute to a better understanding of underlying pathology. Recently, several antibodies became available that recognize markers associated with Treg. FOXP3 is currently considered as the best marker to identify Treg in situ, while GITR has been associated to Treg activity. In the present study we investigated the expression of FOXP3 and GITR in normal skin and in a panel of different inflammatory dermatoses, i.e. spongiotic dermatitis, psoriasis, lichen planus and leishmaniasis. 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 FACS analysis on peripheral blood T cells showed that most FOXP3+ cells expressed GITR and vice versa, whereas a minority was single positive for these markers. The mean frequency of FOXP3+ T cells in spongiotic dermatitis, psoriasis and lichen planus were 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 the inflammatory skin diseases and normal skin, despite the well known differences of the inflammatory conditions under investigation.
Key Words:
regulatory T cells, Treg, inflammation, dermatoses, immunohistochemistry, spectral imaging