Ontogeny of Langerhans cells in human embryonic and fetal skin: cell densities and phenotypic expression relative to epidermal growth

Langerhans cells (LCs) positive for HLA-DR antigens were present in developing human epidermis by at least 7 weeks estimated gestational age (EGA). Most were negative for CD1 (T6) until 12-13 weeks EGA when they underwent a dramatic increase in CD1 reactivity. To gain insight into the density of LCs during ontogeny and to assess whether their distribution was coordinated with epidermal growth, the number of cells positive for both HLA-DR and CD1 antigens was determined relative to surface area and to volume of developing, interfollicular epidermis. LCs differed in their phenotype, distribution (follicular vs. interfollicular), size, and shape between 7 and 21 weeks EGA; however, during this period they maintained a statistically equivalent (P greater than .25) density (65 cells/mm2 and 1,750/mm3) even though the epidermis increased in thickness and the fetus rapidly expanded its surface area. While LCs were evenly distributed within the epidermal sheets at all gestational ages, those in embryonic skin were much smaller and less dendritic than the older cells. The density, size, and shape of LCs in developing skin seemed to be independent of epidermal status (e.g., thickness of keratinization, and number of cell layers) but rather were correlated with gestational age. The number of fetal LCs, through at least 23 weeks EGA, was only 10-20% of the adult LC density. Thus, we can conclude that the increase in LC density to adult levels must occur either during the third trimester or after birth.