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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, Chris M. van der Loos, Peter Teeling, Allard C. van der Wal and Marcel B.M. Teunissen

Departments of Pathology (OJdB,CMvdL,PT,ACvdW) and Dermatology (MBMT), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

Correspondence to: Dr. O.J. de Boer, Department of Pathology, Academic Medical Center, University of Amsterdam, PO Box 22700, 1100 DE Amsterdam, The Netherlands. E-mail: o.j.deboer{at}amc.uva.nl

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 (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. (J Histochem Cytochem 55:891–898, 2007)

Key Words: regulatory T cells • inflammation • dermatoses • immunohistochemistry • spectral imaging

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