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HLA-DR+ leukocytes acquire CD1 antigens in embryonic and fetal human skin and contain functional antigen-presenting cells.

Schuster C, Vaculik C, Fiala C, Meindl S, Brandt O, Imhof M, Stingl G, Eppel W, Elbe-Bürger A - J. Exp. Med. (2009)

Bottom Line: We also found that CD45(+)HLA-DR(high)CD1c(+) dendritic cells (DCs) are already present in the epidermis and dermis at 9 wk estimated gestational age (EGA) and that transforming growth factor beta1 production precedes Langerin and CD1a expression on CD45(+)CD1c(+) Langerhans cell (LC) precursors.Functionally, embryonic antigen-presenting cells (APCs) are able to phagocytose antigen, to up-regulate costimulatory molecules upon culture, and to efficiently stimulate T cells in a mixed lymphocyte reaction.Collectively, our data provide insight into skin DC biology and the mechanisms through which skin DCs presumably populate the skin during development.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, DIAID, 1090 Vienna, Austria.

ABSTRACT
Adequate numbers and functional maturity are needed for leukocytes to exhibit a protective role in host defense. During intrauterine life, the skin immune system has to acquire these prerequisites to protect the newborn from infection in the hostile external environment after birth. We investigated the quantitative, phenotypic, and functional development of skin leukocytes and analyzed the factors controlling their proliferation and trafficking during skin development. We show that CD45(+) leukocytes are scattered in embryonic human skin and that their numbers continuously increase as the developing skin generates an environment that promotes proliferation of skin resident leukocytes as well as the influx of leukocytes from the circulation. We also found that CD45(+)HLA-DR(high)CD1c(+) dendritic cells (DCs) are already present in the epidermis and dermis at 9 wk estimated gestational age (EGA) and that transforming growth factor beta1 production precedes Langerin and CD1a expression on CD45(+)CD1c(+) Langerhans cell (LC) precursors. Functionally, embryonic antigen-presenting cells (APCs) are able to phagocytose antigen, to up-regulate costimulatory molecules upon culture, and to efficiently stimulate T cells in a mixed lymphocyte reaction. Collectively, our data provide insight into skin DC biology and the mechanisms through which skin DCs presumably populate the skin during development.

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HLA-DR+ leukocytes are present in the skin already at 9 wk EGA. (A) Multiparameter flow cytometry of freshly isolated single cells of embryonic, fetal, and adult skin was performed by incubation with mAb against the cell surface markers indicated. Dead cells were excluded by 7-AAD uptake. Quadrants in dot plots were set according to isotype-matched control staining. Dot plots display 60,000 cells and are representative of 5–15 experiments (compare Fig. S2, available at http://www.jem.org/cgi/content/full/jem.20081747/DC1). (B) Immunofluorescence double staining for the markers indicated was performed on cryostat sections of embryonic, fetal, and adult skin. One of at least three experiments per group is shown. Arrows denote CD45+HLA-DRhigh cells and arrowheads denote CD45+HLA-DRlow cells. Bars, 50 μm.
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fig3: HLA-DR+ leukocytes are present in the skin already at 9 wk EGA. (A) Multiparameter flow cytometry of freshly isolated single cells of embryonic, fetal, and adult skin was performed by incubation with mAb against the cell surface markers indicated. Dead cells were excluded by 7-AAD uptake. Quadrants in dot plots were set according to isotype-matched control staining. Dot plots display 60,000 cells and are representative of 5–15 experiments (compare Fig. S2, available at http://www.jem.org/cgi/content/full/jem.20081747/DC1). (B) Immunofluorescence double staining for the markers indicated was performed on cryostat sections of embryonic, fetal, and adult skin. One of at least three experiments per group is shown. Arrows denote CD45+HLA-DRhigh cells and arrowheads denote CD45+HLA-DRlow cells. Bars, 50 μm.

Mentions: In healthy adult skin CD45+ LCs, dermal DCs, macrophages, and a fraction of CD45− endothelial cells express HLA-DR (24, 25). To explore the development of CD45+HLA-DR+ leukocytes, we analyzed embryonic, fetal, and, for comparison, adult skin by flow cytometry. We found that CD45+HLA-DR+ cells are already present in embryonic skin, although in lower frequency than in fetal or in adult skin (Fig. 3 A and Fig. S2 A, available at http://www.jem.org/cgi/content/full/jem.20081747/DC1), thus confirming and extending findings of previous studies (16, 19, 21). In contrast to adult skin, where the majority of CD45+HLA-DR+ leukocytes express high levels of this marker, developing skin shows a continuum of HLA-DRlow to HLA-DRhigh leukocytes. Although HLA-DR expression is restricted to CD45+ leukocytes in embryonic skin, CD45−HLA-DR+ cells were first detected in fetal skin, although less frequently than in adult skin (Fig. 3 A; Fig. S2 B). Immunofluorescence locates CD45+HLA-DRhigh cells in the epidermis and the dermis, whereas CD45+HLA-DRlow cells are found exclusively in the dermis (Fig. 3 B, arrowheads). Using collagen type IV to depict the basement membrane of vessels, we detected CD45−HLA-DR+ cells in fetal and adult skin lining the luminal side of the basement membranes of vessels, thereby confirming their endothelial nature (Fig. S2 C). Keratinocytes show no expression of HLA-DR in all samples investigated.


HLA-DR+ leukocytes acquire CD1 antigens in embryonic and fetal human skin and contain functional antigen-presenting cells.

Schuster C, Vaculik C, Fiala C, Meindl S, Brandt O, Imhof M, Stingl G, Eppel W, Elbe-Bürger A - J. Exp. Med. (2009)

HLA-DR+ leukocytes are present in the skin already at 9 wk EGA. (A) Multiparameter flow cytometry of freshly isolated single cells of embryonic, fetal, and adult skin was performed by incubation with mAb against the cell surface markers indicated. Dead cells were excluded by 7-AAD uptake. Quadrants in dot plots were set according to isotype-matched control staining. Dot plots display 60,000 cells and are representative of 5–15 experiments (compare Fig. S2, available at http://www.jem.org/cgi/content/full/jem.20081747/DC1). (B) Immunofluorescence double staining for the markers indicated was performed on cryostat sections of embryonic, fetal, and adult skin. One of at least three experiments per group is shown. Arrows denote CD45+HLA-DRhigh cells and arrowheads denote CD45+HLA-DRlow cells. Bars, 50 μm.
© Copyright Policy
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC2626673&req=5

fig3: HLA-DR+ leukocytes are present in the skin already at 9 wk EGA. (A) Multiparameter flow cytometry of freshly isolated single cells of embryonic, fetal, and adult skin was performed by incubation with mAb against the cell surface markers indicated. Dead cells were excluded by 7-AAD uptake. Quadrants in dot plots were set according to isotype-matched control staining. Dot plots display 60,000 cells and are representative of 5–15 experiments (compare Fig. S2, available at http://www.jem.org/cgi/content/full/jem.20081747/DC1). (B) Immunofluorescence double staining for the markers indicated was performed on cryostat sections of embryonic, fetal, and adult skin. One of at least three experiments per group is shown. Arrows denote CD45+HLA-DRhigh cells and arrowheads denote CD45+HLA-DRlow cells. Bars, 50 μm.
Mentions: In healthy adult skin CD45+ LCs, dermal DCs, macrophages, and a fraction of CD45− endothelial cells express HLA-DR (24, 25). To explore the development of CD45+HLA-DR+ leukocytes, we analyzed embryonic, fetal, and, for comparison, adult skin by flow cytometry. We found that CD45+HLA-DR+ cells are already present in embryonic skin, although in lower frequency than in fetal or in adult skin (Fig. 3 A and Fig. S2 A, available at http://www.jem.org/cgi/content/full/jem.20081747/DC1), thus confirming and extending findings of previous studies (16, 19, 21). In contrast to adult skin, where the majority of CD45+HLA-DR+ leukocytes express high levels of this marker, developing skin shows a continuum of HLA-DRlow to HLA-DRhigh leukocytes. Although HLA-DR expression is restricted to CD45+ leukocytes in embryonic skin, CD45−HLA-DR+ cells were first detected in fetal skin, although less frequently than in adult skin (Fig. 3 A; Fig. S2 B). Immunofluorescence locates CD45+HLA-DRhigh cells in the epidermis and the dermis, whereas CD45+HLA-DRlow cells are found exclusively in the dermis (Fig. 3 B, arrowheads). Using collagen type IV to depict the basement membrane of vessels, we detected CD45−HLA-DR+ cells in fetal and adult skin lining the luminal side of the basement membranes of vessels, thereby confirming their endothelial nature (Fig. S2 C). Keratinocytes show no expression of HLA-DR in all samples investigated.

Bottom Line: We also found that CD45(+)HLA-DR(high)CD1c(+) dendritic cells (DCs) are already present in the epidermis and dermis at 9 wk estimated gestational age (EGA) and that transforming growth factor beta1 production precedes Langerin and CD1a expression on CD45(+)CD1c(+) Langerhans cell (LC) precursors.Functionally, embryonic antigen-presenting cells (APCs) are able to phagocytose antigen, to up-regulate costimulatory molecules upon culture, and to efficiently stimulate T cells in a mixed lymphocyte reaction.Collectively, our data provide insight into skin DC biology and the mechanisms through which skin DCs presumably populate the skin during development.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, DIAID, 1090 Vienna, Austria.

ABSTRACT
Adequate numbers and functional maturity are needed for leukocytes to exhibit a protective role in host defense. During intrauterine life, the skin immune system has to acquire these prerequisites to protect the newborn from infection in the hostile external environment after birth. We investigated the quantitative, phenotypic, and functional development of skin leukocytes and analyzed the factors controlling their proliferation and trafficking during skin development. We show that CD45(+) leukocytes are scattered in embryonic human skin and that their numbers continuously increase as the developing skin generates an environment that promotes proliferation of skin resident leukocytes as well as the influx of leukocytes from the circulation. We also found that CD45(+)HLA-DR(high)CD1c(+) dendritic cells (DCs) are already present in the epidermis and dermis at 9 wk estimated gestational age (EGA) and that transforming growth factor beta1 production precedes Langerin and CD1a expression on CD45(+)CD1c(+) Langerhans cell (LC) precursors. Functionally, embryonic antigen-presenting cells (APCs) are able to phagocytose antigen, to up-regulate costimulatory molecules upon culture, and to efficiently stimulate T cells in a mixed lymphocyte reaction. Collectively, our data provide insight into skin DC biology and the mechanisms through which skin DCs presumably populate the skin during development.

Show MeSH
Related in: MedlinePlus