Immunohistochemical analysis of regulatory T cell markers FOXP3 and GITR on CD4+CD25+ T cells in normal skin and inflammatory dermatoses.
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.
de Boer
Onno J
OJ
Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. o.j.deboer@amc.uva.nl
van der Loos
Chris M
CM
Teeling
Peter
P
van der Wal
Allard C
AC
Teunissen
Marcel B M
MB
D015415:Biomarkers / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism*; D017449:Dermatitis, Allergic Contact / Q000276:immunology / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D053450:Glucocorticoid-Induced TNFR-Related Protein; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D007896:Leishmaniasis / Q000276:immunology / Q000378:metabolism; D008010:Lichen Planus / Q000276:immunology / Q000378:metabolism; D011565:Psoriasis / Q000276:immunology / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D012867:Skin / Q000276:immunology* / Q000378:metabolism; D012871:Skin Diseases / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
D015415:Biomarkers; D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053450:Glucocorticoid-Induced TNFR-Related Protein; D053645:Interleukin-2 Receptor alpha Subunit; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C491405:TNFRSF18 protein, human