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Phenotypic characterization of leukocytes in prenatal human dermis.

Schuster C, Vaculik C, Prior M, Fiala C, Mildner M, Eppel W, Stingl G, Elbe-Bürger A - J. Invest. Dermatol. (2012)

Bottom Line: By flow cytometry and immunofluorescence, we found a distinction between CD206(+)CD1c(+)CD11c(+) DDCs and CD206(+)CD209(+)CD1c(-) skin macrophages by 9 weeks estimated gestational age (EGA).During midgestation, CD3(+)FoxP3(-) and CD3(+)FoxP3(+) cells can exclusively be found in the dermis.Our data show at which time point during gestation antigen-presenting cells, T cells, and mast cells populate the human dermis and provide a step forward to a better understanding of the development of the human skin immune system.

View Article: PubMed Central - PubMed

Affiliation: Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, Medical University of Vienna, Vienna, Austria.

ABSTRACT
The adult human skin harbors a variety of leukocytes providing immune surveillance and host defense, but knowledge about their ontogeny is scarce. In this study we investigated the number and phenotype of leukocytes in prenatal human skin (dermal dendritic cells (DDCs), macrophages, T cells (including FoxP3(+) regulatory T cells), and mast cells) to unravel their derivation and to get a clue as to their putative function in utero. By flow cytometry and immunofluorescence, we found a distinction between CD206(+)CD1c(+)CD11c(+) DDCs and CD206(+)CD209(+)CD1c(-) skin macrophages by 9 weeks estimated gestational age (EGA). T cells appear at the end of the first trimester, expressing CD3 intracytoplasmatically. During midgestation, CD3(+)FoxP3(-) and CD3(+)FoxP3(+) cells can exclusively be found in the dermis. Similarly, other leukocytes such as CD117(+) (c-kit) mast cells were not identified before 12-14 weeks EGA and only slowly acquire a mature phenotype during gestation. Our data show at which time point during gestation antigen-presenting cells, T cells, and mast cells populate the human dermis and provide a step forward to a better understanding of the development of the human skin immune system.

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FoxP3+ T cells are present in fetal human skin. Immunofluorescence double staining was performed on cryostat sections of fetal skin (n=5). Arrows denote CD3+FoxP3− T cells (left panel) and CD3+FoxP3+ T cells (middle panel). Arrowheads indicate intracellular FoxP3 staining in the insert. Demonstration of a FoxP3+ and a FoxP3− T cell on the same section (right panel). Bars=50 μm, bar in inset=20 μm. DAPI, 4,6-diamidino-2-phenylindole; EGA, estimated gestational age.
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fig5: FoxP3+ T cells are present in fetal human skin. Immunofluorescence double staining was performed on cryostat sections of fetal skin (n=5). Arrows denote CD3+FoxP3− T cells (left panel) and CD3+FoxP3+ T cells (middle panel). Arrowheads indicate intracellular FoxP3 staining in the insert. Demonstration of a FoxP3+ and a FoxP3− T cell on the same section (right panel). Bars=50 μm, bar in inset=20 μm. DAPI, 4,6-diamidino-2-phenylindole; EGA, estimated gestational age.

Mentions: Given the key role of regulatory T cells controlling and maintaining tolerance to self-antigens and the linkage of FoxP3 to this function, we further investigated whether these cells may already be present in prenatal skin. Indeed, FoxP3 expression was found in 20.0% (SD 6.5% n=5) of all T cells (5.9 CD3+ cells cm−1, SD 2.9; n=5), a frequency comparable to what is found in the adult skin (Figure 5; Clark and Kupper, 2007; Agius et al., 2009).


Phenotypic characterization of leukocytes in prenatal human dermis.

Schuster C, Vaculik C, Prior M, Fiala C, Mildner M, Eppel W, Stingl G, Elbe-Bürger A - J. Invest. Dermatol. (2012)

FoxP3+ T cells are present in fetal human skin. Immunofluorescence double staining was performed on cryostat sections of fetal skin (n=5). Arrows denote CD3+FoxP3− T cells (left panel) and CD3+FoxP3+ T cells (middle panel). Arrowheads indicate intracellular FoxP3 staining in the insert. Demonstration of a FoxP3+ and a FoxP3− T cell on the same section (right panel). Bars=50 μm, bar in inset=20 μm. DAPI, 4,6-diamidino-2-phenylindole; EGA, estimated gestational age.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3472563&req=5

fig5: FoxP3+ T cells are present in fetal human skin. Immunofluorescence double staining was performed on cryostat sections of fetal skin (n=5). Arrows denote CD3+FoxP3− T cells (left panel) and CD3+FoxP3+ T cells (middle panel). Arrowheads indicate intracellular FoxP3 staining in the insert. Demonstration of a FoxP3+ and a FoxP3− T cell on the same section (right panel). Bars=50 μm, bar in inset=20 μm. DAPI, 4,6-diamidino-2-phenylindole; EGA, estimated gestational age.
Mentions: Given the key role of regulatory T cells controlling and maintaining tolerance to self-antigens and the linkage of FoxP3 to this function, we further investigated whether these cells may already be present in prenatal skin. Indeed, FoxP3 expression was found in 20.0% (SD 6.5% n=5) of all T cells (5.9 CD3+ cells cm−1, SD 2.9; n=5), a frequency comparable to what is found in the adult skin (Figure 5; Clark and Kupper, 2007; Agius et al., 2009).

Bottom Line: By flow cytometry and immunofluorescence, we found a distinction between CD206(+)CD1c(+)CD11c(+) DDCs and CD206(+)CD209(+)CD1c(-) skin macrophages by 9 weeks estimated gestational age (EGA).During midgestation, CD3(+)FoxP3(-) and CD3(+)FoxP3(+) cells can exclusively be found in the dermis.Our data show at which time point during gestation antigen-presenting cells, T cells, and mast cells populate the human dermis and provide a step forward to a better understanding of the development of the human skin immune system.

View Article: PubMed Central - PubMed

Affiliation: Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, Medical University of Vienna, Vienna, Austria.

ABSTRACT
The adult human skin harbors a variety of leukocytes providing immune surveillance and host defense, but knowledge about their ontogeny is scarce. In this study we investigated the number and phenotype of leukocytes in prenatal human skin (dermal dendritic cells (DDCs), macrophages, T cells (including FoxP3(+) regulatory T cells), and mast cells) to unravel their derivation and to get a clue as to their putative function in utero. By flow cytometry and immunofluorescence, we found a distinction between CD206(+)CD1c(+)CD11c(+) DDCs and CD206(+)CD209(+)CD1c(-) skin macrophages by 9 weeks estimated gestational age (EGA). T cells appear at the end of the first trimester, expressing CD3 intracytoplasmatically. During midgestation, CD3(+)FoxP3(-) and CD3(+)FoxP3(+) cells can exclusively be found in the dermis. Similarly, other leukocytes such as CD117(+) (c-kit) mast cells were not identified before 12-14 weeks EGA and only slowly acquire a mature phenotype during gestation. Our data show at which time point during gestation antigen-presenting cells, T cells, and mast cells populate the human dermis and provide a step forward to a better understanding of the development of the human skin immune system.

Show MeSH