title: Restricted expression of transgenic HLA-DRA gene in thymic epithelial cells and its role in acquisition of T cell tolerance to self-superantigens and processed DR alpha-derived peptide.
abstract: We have established a set of transgenic mouse lines in which the HLA-DRA gene was expressed in different cell types. In one line (DR alpha-24), DR alpha E beta b molecules were expressed on thymic medullary and cortical epithelial cells and all lineages of bone marrow-derived antigen-presenting cells (APC) except for thymic macrophages. By contrast, expression of the molecules in another line (DR alpha-30) was found on thymic medullary and cortical epithelial cells but not on bone marrow-derived APC in the thymus and periphery. To evaluate the role of thymic epithelial cells in acquisition of T cell tolerance, comparative analysis of DR alpha-24 and DR alpha-30 was performed. In DR alpha-30, T cells expressing TcR V beta 5 and V beta 11 were eliminated to comparable levels to those in DR alpha-24, suggesting that expression of the DR alpha E beta b molecules on thymic epithelial cells are sufficient for clonal deletion of the self-superantigen-reactive T cells. In addition, CD4+ T cells from DR alpha-30 as well as those from DR alpha-24 were tolerant to DR alpha-derived peptide/I-Ab complex expressed on spleen cells from DR alpha-24 even in the presence of exogenous interleukin-2. These observations suggest that expression of the DR alpha chain in thymic epithelial cells could induce T cell tolerance directed toward naturally processed DR alpha-derived peptide bound to I-Ab molecules, probably via clonal deletion of the self-reactive T cells.
authors.affiliation: Department of Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Fukui
authors.forename: K
authors.initials: K
authors.lastname: Yamamoto
authors.forename: N
authors.initials: N
authors.lastname: Yokoyama
authors.forename: T
authors.initials: T
authors.lastname: Iwanaga
authors.forename: C
authors.initials: C
authors.lastname: Kurashima
authors.forename: Y
authors.initials: Y
authors.lastname: Esaki
authors.forename: A
authors.initials: A
authors.lastname: Kimura
authors.forename: T
authors.initials: T
authors.lastname: Akashi
authors.forename: K
authors.initials: K
authors.lastname: Hirokawa
authors.forename: T
authors.initials: T
authors.lastname: Sasazuki
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003574:Cytochrome c Group / Q000276:immunology; D004848:Epithelium / Q000276:immunology; D005260:Female; D015870:Gene Expression; D005796:Genes; D006684:HLA-DR Antigens / Q000235:genetics* / Q000276:immunology; D059805:HLA-DR alpha-Chains; D006801:Humans; D007108:Immune Tolerance; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
chemical_list: D001324:Autoantigens; D003574:Cytochrome c Group; D006684:HLA-DR Antigens; D059805:HLA-DR alpha-Chains; D010455:Peptides; D012333:RNA, Messenger