HLA-G in the human thymus: a subpopulation of medullary epithelial but not CD83(+) dendritic cells expresses HLA-G as a membrane-bound and soluble protein

Abstract

The human MHC class Ib gene HLA-G is transcribed and translated in different placental cell subpopulations during pregnancy. In addition to this restricted tissue distribution, HLA-G proteins were also recently detected in the thymus of HLA-G transgenic mice, as well as in some human thymic epithelial cells (TEC). There was a need to further define the phenotype of the HLA-G-expressing cells in the human thymus as well as the type of translated forms that they produce. Using several HLA-G-specific mAb and immunohistochemistry performed on cryosections of human thymi at different ages, we found that the HLA-G-expressing cells are present on medullary cells exhibiting the epithelial morphological type 6. Co-localization experiments performed by double or triple immunofluorescence staining demonstrate that these HLA-G-expressing cells express various cytokeratins, epithelial cell markers but not the CD83 dendritic cell marker. We further show by ELISA measurements that a subset of primary cultured human TEC also expresses soluble HLA-G. Therefore, HLA-G protein tissue distribution is not restricted solely to placental cells. A subpopulation of medullary TEC also expresses HLA-G both at their cell surface and in secreted form, raising the question of the functional significance of such MHC class Ib molecules. Whether thymic soluble and/or membrane-bound HLA-G contribute to inhibit NK cells or to a negative selection of autoreactive T cells which could be harmful in case of pregnancy and/or to a positive selection of viral peptides/HLA-G-restricted CD8(+) T cells remains to be demonstrated.