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.
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.
Mallet
V
V
INSERM U395, CHU Purpan, BP 3028, 31024 Toulouse Cedex 3, France.
Blaschitz
A
A
Crisa
L
L
Schmitt
C
C
Fournel
S
S
King
A
A
Loke
Y W
YW
Dohr
G
G
Le Bouteiller
P
P
D000293:Adolescent; D015703:Antigens, CD; D015415:Biomarkers; D002648:Child; D002675:Child, Preschool; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D006680:HLA Antigens / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis* / Q000276:immunology; D007231:Infant, Newborn; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000276:immunology; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D012995:Solubility; D013950:Thymus Gland / Q000033:anatomy & histology / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D014158:Transcription, Genetic / Q000276:immunology; D000097802:CD83 Antigen
D015703:Antigens, CD; D015415:Biomarkers; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D000097802:CD83 Antigen