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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

1999; Oxford University Press; Volume: 11; Issue: 6 Linguagem: Inglês

10.1093/intimm/11.6.889

1460-2377

Valérie Mallet, Astrid Blaschitz, Laura Crisá, Christian Schmitt, Sylvie Fournel, Ashley King, Y.W. Loke, Gottfried Dohr, Philippe Le Bouteiller,

Immunotherapy and Immune Responses

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.