Intercellular MHC transfer between thymic epithelial and dendritic cells.
Thymic dendritic cells (DC) and epithelial cells play a major role in central tolerance but their respective roles are still controversial. Epithelial cells have the unique ability to ectopically express peripheral tissue-restricted antigens conferring self-tolerance to tissues. Paradoxically, while negative selection seems to occur for some of these antigens, epithelial cells, contrary to DC, are poor negative selectors. Using a thymic epithelial cell line, we show the functional intercellular transfer of membrane material, including MHC molecules, occurring between epithelial cells. Using somatic and bone marrow chimeras, we show that this transfer occurs efficiently in vivo between epithelial cells and, in a polarized fashion, from epithelial to DC. This novel mode of transfer of MHC-associated, epithelial cell-derived self-antigens onto DC might participate to the process of negative selection in the thymic medulla.
Millet
Virginie
V
Aix Marseille Université, Faculté des Sciences de Luminy, Centre d'Immunologie de Marseille-Luminy, Marseille, France.
Naquet
Philippe
P
Guinamard
Rodolphe R
RR
D000581:Amidohydrolases / Q000378:metabolism; D000818:Animals; D000941:Antigens / Q000276:immunology / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000032:analysis; D001692:Biological Transport / Q000276:immunology*; D016026:Bone Marrow Transplantation; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology*; D002460:Cell Line; D002678:Chimera / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D000071858:Epithelial Cell Adhesion Molecule; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D005456:Fluorescent Dyes / Q000378:metabolism; D058851:GPI-Linked Proteins; D006183:H-2 Antigens / Q000235:genetics / Q000378:metabolism; D006649:Histocompatibility Antigens / Q000235:genetics / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D011554:Pseudopodia / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology
D000941:Antigens; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; D005456:Fluorescent Dyes; D058851:GPI-Linked Proteins; D006183:H-2 Antigens; D006649:Histocompatibility Antigens; D000949:Histocompatibility Antigens Class II; D000581:Amidohydrolases; C022314:pantetheinase