HLA-G in the human thymus: a subpopulation of medullary epithelial but notCD83(+) dendritic cells expresses HLA-G as a membrane-bound and soluble protein

The human MHC class Ib gene HLA-G is transcribed and translated in differen t placental cell subpopulations during pregnancy. In addition to this restr icted tissue distribution, HLA-G proteins were also recently detected in th e thymus of HLA-G transgenic mice, as well as in some human thymic epitheli al cells (TEG), 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 f orms that they produce. Using several HLA-G-specific mAb and immunohistoche mistry 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, Go-localization experiments performed by double or triple immunofluorescence staining demonstrate that these HLA- G-expressing cells express various cytokeratins, epithelial cell markers bu t not the GD83 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 pl acental cells. A subpopulation of medullary TEC also expresses HLA-G both a t their cell surface and in secreted form, raising the question of the func tional 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 pregna ncy and/or to a positive selection of viral peptides/HLA-G-restricted CD8() T cells remains to be demonstrated.